The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from ...The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from a Han population in North China, and determined the peripheral blood angiotensin-converting enzyme genotype using PCR-restriction fragment length polymorphism analysis. The results showed that the frequencies of the DD genotype and D allele were increased in patients with middle cerebral artery stenosis, but the difference was not statistically significant compared with healthy controls. The findings of this study on the relationship between stroke genes and middle cerebral artery stenosis indicate no significant correlation between the frequencies of the DO genotype and D allele of angiotensin-converting enzyme and middle cerebral artery stenosis in this Han population from North China. In the future, studies will be carried out to investigate correlations between multiple stroke candidate gene synergy and middle cerebral artery stenosis to provide a foundation for the development of gene therapy.展开更多
This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN case...This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.展开更多
To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD ...To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (≥75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A→C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P〈0.001). The frequency of the ATIR A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P〉0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P〉0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P〈0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.展开更多
AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACE...AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.展开更多
Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearin...Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.展开更多
Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of reg...Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.展开更多
Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),an...Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.展开更多
AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHOD...AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.展开更多
Objective To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine patients with T2DM di...Objective To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-trip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated. Results The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (χ^2=7.61, P=0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels. Conclusion The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.展开更多
Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hy...Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM. Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CO of variations of ACE2 for HCM. Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95%C/ 1.01-1.77, P=0.04; OR 1.11, 95%C/ 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95%C/1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=0.04, respectively). No association was found between the two polymorphisms with female patients with HCM. Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.展开更多
Objective To investigate the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism and the clinico pathological manifestations in patients with immunoglobulin nephropathy (...Objective To investigate the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism and the clinico pathological manifestations in patients with immunoglobulin nephropathy (IgAN). Methods A flanking primer pair and an insertion specific primer pair were used to perform two polymerase chain reactions so as to analyse the insertion/deletion polymorphism of ACE gene. Results There was a significantly higher genotype fre quency for DD genotype in IgAN patients. The frequencies for DD genotype were also higher in those patients with hypertension and/or heavy proteinuria and/or severe glomerular sclerosis (P<0.05). Conclusions We observed a significant association of the deletion polymorphism of ACE gene with renal insufficiency, hypertension and severe glomerular lesions at biopsy. The deletion allele may play a role, at least to some extent, in the deterioration and progression in IgA nephropathy.展开更多
Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive...Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P <0.05). Carotid internal diameter,distensibility and stiffness were similar among the DD,ID and II genotypes of ACE ( P >0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%,and 79.5% vs 40.5%,respectively, P <0.001). In multiple stepwise regression analysis,independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes ( P <0.001),age ( P <0.001) and carotid internal diameter ( P =0.032). Moreover,triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype ( P <0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT,but not to internal diameter,distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.展开更多
Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain contr...Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95% confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.展开更多
AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han populatio...AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the genealcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence in- terval (CI): 2.76-5.67]. Signif icant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00,95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/ Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.展开更多
Heart diseases are the main cause of mortality in Mexico, being coronary </span><span style="font-family:Verdana;">heart disease the most frequent in the country. Its high prevalence makes i...Heart diseases are the main cause of mortality in Mexico, being coronary </span><span style="font-family:Verdana;">heart disease the most frequent in the country. Its high prevalence makes important </span><span style="font-family:Verdana;">the study of the pathophysiology and the search for prognostic </span><span style="font-family:Verdana;">factors. Different genes and polymorphisms promote atherogenesis and coronary artery disease, they affect inflammatory and vascular pathological processes. </span><span style="font-family:Verdana;">Interferon regulatory factor 5 (IRF5) is associated with coronary heart disease, it promotes chronic inflammation and cytokines release;it could trigger immune reactions and its activating receptors express in the vascular endothelium. Besides, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are implied with coronary disease, they are found in angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) genes. These genetic polymorphisms are associated with a prothrombotic state, endothelial dysfunction, and immune activation. Multiple experimental studies showed that chronic activation of RAAS and chronic expression of IRF5 generates an environment prone to the development of atherosclerosis, and autoimmune and cardiovascular diseases. Studying these specific genes and their relationship with coronary heart disease will allow a better understanding of the pathological process and possibly the quest for new treatments.展开更多
Background Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in β1-adrenergic receptor and blood pressure (BP), little was know...Background Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in β1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I) / deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients, Methods Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment. Results The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P=0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR. Conclusions The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding展开更多
To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1,CYP2D6,GSTM1,GSTT1,and GSTP1 and idiopathic male infertility.By observing the efficacy of antioxidants in the treatment of ...To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1,CYP2D6,GSTM1,GSTT1,and GSTP1 and idiopathic male infertility.By observing the efficacy of antioxidants in the treatment of idiopathic male infertility,the effect of metabolic enzyme gene polymorphisms on antioxidant therapy in patients with idiopathic male infertility was prospectively studied.This case-control study included 310 men with idiopathic infertility and 170 healthy controls.The cytochrome P4501A1(CYP1A1),cytochrome P4502D6(CYP2D6),glutathione S-transferase M1(GSTM1),glutathione S-transferase T1(GSTT1),and glutathione S-transferase P1(GSTP1)genotypes in peripheral blood samples were analyzed by polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP).The idiopathic male infertility group was treated with vitamin C,vitamin E,and coenzyme Q10 for 3 months and followed up for 6 months.GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)in the idiopathic male infertility groups were more common than those in the control group.The sperm concentration,motility,viability,mitochondrial membrane potential(MMP),and seminal plasma total antioxidant capacity(T-AOC)level in patients with GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)were lower than those in wild-type carriers,and the sperm DNA fragmentation index(DFI),8-hydroxy-2'-deoxyguanosine(8-OH-dG),and malondialdehyde(MDA)and nitric oxide(NO)levels were higher.Therefore,oxidative damage may play an important role in the occurrence and development of idiopathic male infertility,but antioxidant therapy is not effective in male infertility patients with GSTM1 and GSTT1 gene deletions.展开更多
Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand o...Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand obesity in Chinese type 2 diabetic mellitus(T2DM) using an improved experiment method. MethodsFrom June 2016 to March 2018,300 T2DM patientswith DKD [DKD( +)]and 300 T2DM patients withoutDKD [DKD ( - )] were selected from China-JapanFriendship Hospital. The improved Triple Primer Methodthat combined PCR with capillary electrophoresis was establishedin this study to detect the ACE genotype. Therelevant clinical data as well as the frequencies of genotypeand allele of ACE gene I /D polymorphism betweenthe two groups were statistically analyzed. Patients werefurther grouped based on smoking status and obesity formultivariate regression.展开更多
文摘The angiotensin-converting enzyme gene is a candidate gene of stroke. The present study involved 62 healthy volunteers and 148 patients with middle cerebral artery stenosis as confirmed by brain color ultrasound from a Han population in North China, and determined the peripheral blood angiotensin-converting enzyme genotype using PCR-restriction fragment length polymorphism analysis. The results showed that the frequencies of the DD genotype and D allele were increased in patients with middle cerebral artery stenosis, but the difference was not statistically significant compared with healthy controls. The findings of this study on the relationship between stroke genes and middle cerebral artery stenosis indicate no significant correlation between the frequencies of the DO genotype and D allele of angiotensin-converting enzyme and middle cerebral artery stenosis in this Han population from North China. In the future, studies will be carried out to investigate correlations between multiple stroke candidate gene synergy and middle cerebral artery stenosis to provide a foundation for the development of gene therapy.
文摘This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.
文摘To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (≥75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A→C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P〈0.001). The frequency of the ATIR A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P〉0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P〉0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P〈0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.
文摘AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.
基金supported by The Coordinatorship of Scientific Research Projects Department,Süleyman Demirel University(Grant Number:TTU-2021-8402).
文摘Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.
文摘Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.
基金This work was supported by National Natural Science Foundation of China (No.81560502), Newcomer Award for Doctoral Student in Yunnan Province (No.601152706) and PhD Innovation Fund of Kunming Medical University (No.2017D004).
文摘Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.
基金Supported by Department of Biotechnology,Government of India,New Delhi(DBT Project),No.BT/PR 4640/MED/30/716/2012
文摘AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.
基金This study was supported by the Capital Development Fund Project (Grant No. 2002-1017)
文摘Objective To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-trip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated. Results The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (χ^2=7.61, P=0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels. Conclusion The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.
文摘Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM. Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CO of variations of ACE2 for HCM. Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95%C/ 1.01-1.77, P=0.04; OR 1.11, 95%C/ 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95%C/1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=0.04, respectively). No association was found between the two polymorphisms with female patients with HCM. Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.
文摘Objective To investigate the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism and the clinico pathological manifestations in patients with immunoglobulin nephropathy (IgAN). Methods A flanking primer pair and an insertion specific primer pair were used to perform two polymerase chain reactions so as to analyse the insertion/deletion polymorphism of ACE gene. Results There was a significantly higher genotype fre quency for DD genotype in IgAN patients. The frequencies for DD genotype were also higher in those patients with hypertension and/or heavy proteinuria and/or severe glomerular sclerosis (P<0.05). Conclusions We observed a significant association of the deletion polymorphism of ACE gene with renal insufficiency, hypertension and severe glomerular lesions at biopsy. The deletion allele may play a role, at least to some extent, in the deterioration and progression in IgA nephropathy.
文摘Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P <0.05). Carotid internal diameter,distensibility and stiffness were similar among the DD,ID and II genotypes of ACE ( P >0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%,and 79.5% vs 40.5%,respectively, P <0.001). In multiple stepwise regression analysis,independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes ( P <0.001),age ( P <0.001) and carotid internal diameter ( P =0.032). Moreover,triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype ( P <0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT,but not to internal diameter,distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.
文摘Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95% confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.
基金Supported by The National Natural Science Foundation of China, No. 30901726
文摘AIM: To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. METHODS: Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the genealcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. RESULTS: Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence in- terval (CI): 2.76-5.67]. Signif icant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00,95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/ Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). CONCLUSION: The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.
文摘Heart diseases are the main cause of mortality in Mexico, being coronary </span><span style="font-family:Verdana;">heart disease the most frequent in the country. Its high prevalence makes important </span><span style="font-family:Verdana;">the study of the pathophysiology and the search for prognostic </span><span style="font-family:Verdana;">factors. Different genes and polymorphisms promote atherogenesis and coronary artery disease, they affect inflammatory and vascular pathological processes. </span><span style="font-family:Verdana;">Interferon regulatory factor 5 (IRF5) is associated with coronary heart disease, it promotes chronic inflammation and cytokines release;it could trigger immune reactions and its activating receptors express in the vascular endothelium. Besides, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are implied with coronary disease, they are found in angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) genes. These genetic polymorphisms are associated with a prothrombotic state, endothelial dysfunction, and immune activation. Multiple experimental studies showed that chronic activation of RAAS and chronic expression of IRF5 generates an environment prone to the development of atherosclerosis, and autoimmune and cardiovascular diseases. Studying these specific genes and their relationship with coronary heart disease will allow a better understanding of the pathological process and possibly the quest for new treatments.
文摘Background Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in β1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I) / deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients, Methods Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment. Results The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P=0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR. Conclusions The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding
基金supported by the National Natural Science Fund of China(No.81660263 and No.81300541)the China Postdo.ctoral Science Foundation(No.2015M582760XB)the Doctoral Fund of Affiliated Hospital of Guiyang Medical College(No.C-2012-6).
文摘To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1,CYP2D6,GSTM1,GSTT1,and GSTP1 and idiopathic male infertility.By observing the efficacy of antioxidants in the treatment of idiopathic male infertility,the effect of metabolic enzyme gene polymorphisms on antioxidant therapy in patients with idiopathic male infertility was prospectively studied.This case-control study included 310 men with idiopathic infertility and 170 healthy controls.The cytochrome P4501A1(CYP1A1),cytochrome P4502D6(CYP2D6),glutathione S-transferase M1(GSTM1),glutathione S-transferase T1(GSTT1),and glutathione S-transferase P1(GSTP1)genotypes in peripheral blood samples were analyzed by polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP).The idiopathic male infertility group was treated with vitamin C,vitamin E,and coenzyme Q10 for 3 months and followed up for 6 months.GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)in the idiopathic male infertility groups were more common than those in the control group.The sperm concentration,motility,viability,mitochondrial membrane potential(MMP),and seminal plasma total antioxidant capacity(T-AOC)level in patients with GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)were lower than those in wild-type carriers,and the sperm DNA fragmentation index(DFI),8-hydroxy-2'-deoxyguanosine(8-OH-dG),and malondialdehyde(MDA)and nitric oxide(NO)levels were higher.Therefore,oxidative damage may play an important role in the occurrence and development of idiopathic male infertility,but antioxidant therapy is not effective in male infertility patients with GSTM1 and GSTT1 gene deletions.
文摘Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand obesity in Chinese type 2 diabetic mellitus(T2DM) using an improved experiment method. MethodsFrom June 2016 to March 2018,300 T2DM patientswith DKD [DKD( +)]and 300 T2DM patients withoutDKD [DKD ( - )] were selected from China-JapanFriendship Hospital. The improved Triple Primer Methodthat combined PCR with capillary electrophoresis was establishedin this study to detect the ACE genotype. Therelevant clinical data as well as the frequencies of genotypeand allele of ACE gene I /D polymorphism betweenthe two groups were statistically analyzed. Patients werefurther grouped based on smoking status and obesity formultivariate regression.