Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

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.

Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

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.

Interaction and Relationship Between Angiotensin ConvertingEnzyme Gene and Environmental Factors Predisposing toEssential Hypertension in MongolianPopulation of China

Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

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.

Association of Polymorphisms in Angiotensin-converting Enzyme and Type 1 Angiotensin Ⅱ Receptor Genes with Coronary Heart Disease and the Severity of Coronary Artery Stenosis

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.

Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis

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.

Association of Angiotensin Converting Enzyme Gene I/D Polymorphism With Type 2 Diabetes Mellitus

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.

Angiotensin-converting enzyme gene polymorphism and middle cerebral artery stenosis in a Chinese Han population

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.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

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.

Angiotensin Ⅰ-converting enzyme gene poly morphism in Chinese patientswith obstructive sleep apnea syndrome

Objective To investigate the relationship of an insertion/deletion (I/D) polymorphism of the angiotension converting enzyme (ACE) gene to obstructive sleep apnea syndrome (OSAS) patients and the control subjects.Methods Genomic DNA was extracted from blood samples and amplified by polymerase chain reaction (PCR). PCR primers flanked the polymorphic region in intro 16 of the ACE gene. Results OSAS patients had significantly higher frequencies of I/I genotype and insertion allele of the ACE gene as compared with the control subjects in Chinese population. The OSAS patients with I/I genotype had significantly longer apnea time, lower minimum SaO2 and greater AHI than the OSAS patients with I/D genotype. Conclusion These results indicate that the I/I genotype and I allele are a risk factor for OSAS in Chinese.

Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy

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.

Carotid remodeling of hypertensive subjects and polymorphism of the angiotensin-converting enzyme gene

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.

血管紧张素转化酶基因突变相关的羊水过少胎儿一例遗传学分析

目的:明确一例羊水过少胎儿的遗传学病因。方法:妊娠22^(+2)周对胎儿行超声检查发现羊水指数30 mm并双肾回声稍增,予以低分子量肝素和羊膜腔灌注4周余,胎儿羊水指数未改善。妊娠26^(+6)周超声检查示羊水指数43 mm并双肾回声增强,胎儿父母要求终止妊娠。取引产后的胎儿皮肤及父母外周血行全外显子组测序。结果:全外显子组测序和Sanger测序显示父母携带ACE基因c.1028G>A(p.Trp343X)杂合突变。胎儿携带血管紧张素转化酶(ACE)基因c.1028G>A(p.Trp343X)纯合突变,该突变来源于正常表型的父母。结论:特发性羊水过少可能与ACE基因突变相关的肾小管发育不良有关。

ADRB1和ACE基因多态性与左心室肥厚的相关性研究

目的探讨原发性高血压(EH)左心室肥厚(LVH)患者中β1肾上腺素受体(ADRB1)、血管紧张素转换酶(ACE)基因多态性的作用。方法根据《中国高血压防治指南》(2018年修订版)选取EH住院患者80例,对EH患者进行心脏超声检查,分为LVH(LVH+)组33例和非LVH(LVH-)组47例。收集两组患者临床资料,取外周血使用基因芯片技术检测各自的基因多态性位点,比较两组患者性别、年龄、体重指数、肝肾功能、血糖、血脂以及基因型和等位基因频率。结果两组间性别、年龄、体重指数、空腹血糖、高密度脂蛋白胆固醇、肝功能及血压等比较无显著性差异(P>0.05)。LVH+组ADRB1 CC基因型及C等位基因频率高于LVH-组(P<0.05),LVH+组ACE ID基因型频率及D等位基因频率高于LVH-组(P<0.05)。ADRB1与ACE敏感基因型联合分析,联合基因型分布频率在LVH+组与LVH-组间无显著性差异(P>0.05)。结论ADRB1 C/G多态性与LVH发病相关,CC基因型及C等位基因携带可能是LVH发病危险因素;ACE I/D多态性与LVH发病相关,ID基因型及D等位基因携带可能是LVH发病危险因素;ADRB1与ACE基因的敏感基因型联合作用对LVH发病可能无协同作用。

ACE、ApoE基因多态性与高血压患者冠状动脉狭窄程度的相关性研究

目的探讨血管紧张素转换酶(angiotensin converting enzyme,ACE)、载脂蛋白E(apolipoprotein E,ApoE)基因多态性与高血压患者冠状动脉狭窄程度的相关性。方法选取2019年1月至2022年2月浙江省中医院收治的180例高血压患者作为研究对象,根据其是否患有冠心病(coronary heart disease,CHD)分为对照组(n=85)和CHD组(n=95),同时根据冠状动脉造影结果将CHD组分为单支病变组(n=25)及多支病变组(n=70),统计并比较单支病变组与多支病变组ACE基因型、ApoE基因型与等位基因频率的分布,不同冠状动脉病变程度组别ACE基因多态性、Apo E基因多态性分布情况。结果多支病变组ACE DD基因型频率和ACE D等位基因的频率均显著高于单支病变组(P<0.05);多支病变组ACEⅡ和ACE ID基因型频率均显著低于ACE DD基因型(P<0.05);多支病变组ACE D等位基因频率显著高于ACEⅠ等位基因(P<0.05)。多支病变组ApoE4等位基因频率显著高于单支病变组(P<0.05);两组的ApoE2/E2、ApoE2/E3、ApoE2/E4、ApoE3/E4及ApoE4/E4基因型频率均显著低于同组ApoE3/E3基因型(P<0.05);两组的ApoE2、Apo E4等位基因频率均显著低于同组Apo E3等位基因(P<0.05)。多支病变组ACE DD基因型频率和ACE D等位基因的频率均显著高于单支病变组(P<0.05);多支病变组ACEⅡ和ACE ID基因型频率均显著低于ACE DD基因型(P<0.05);多支病变组ACED等位基因频率显著高于ACEⅠ等位基因(P<0.05)。3组不同冠状动脉病变程度组的ApoE2/E2、ApoE2/E3、ApoE2/E4、ApoE3/E4、ApoE4/E4的基因型频率均显著低于ApoE3/E3基因型(P<0.05)。结论ACE、Apo E基因多态性与高血压患者冠状动脉病变范围及病变程度密切相关。

壮族与汉族原发性高血压患者ACE及CYP3A5基因多态性的关系分析

目的 探讨壮族人群和汉族人群原发性高血压与血管紧张素转化酶(ACE)及细胞色素P450 3A5(CYP3A5)基因分布频率的关系,并将两个民族原发性高血压人群的ACE及CYP3A5基因分布频率进行对比,为精准治疗原发性高血压提供新的临床依据。方法 选取400例原发性高血压患者(壮族病例组200例,汉族病例组200例)为研究对象,采用实时荧光定量聚合酶链反应对ACE基因及CYP3A5基因的多态性进行检测。结果 壮族病例组与汉族病例组中ACE及CYP3A5基因型频率及等位基因分布频率比较,差异均无统计学意义(P>0.05)。壮族病例组中不同性别间ACE及CYP3A5的基因型频率及等位基因分布频率比较,差异均无统计学意义(P>0.05)。汉族病例组中不同性别之间ACE的基因型频率及等位基因分布频率比较,差异有统计学意义(P<0.01),CYP3A5的基因型频率及等位基因分布频率比较,差异均无统计学意义(P>0.05)。相同性别不同民族之间ACE及CYP3A5的基因型频率及等位基因分布频率比较,差异均无统计学意义(P>0.05)。结论 壮族与汉族原发性高血压患者ACE及CYP3A5基因多态性与民族并无明显关联。

ACE2基因缺失对止血带休克后主动脉收缩反应性的影响

目的:观察血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)基因缺失对止血带休克(tourniquet shock,TS)小鼠主动脉收缩反应性的影响。方法:8月龄C57BL/6雄性小鼠,分为野生型(WT)对照组、WT-TS组、基因敲除(knockout,KO)组、KO-TS组,每组10只小鼠,其中5只小鼠血管用于测定血管反应性,另外5只用于其他检测。WT-TS组和KO-TS组小鼠用止血带造成双后肢缺血2 h再灌注4 h后处死。WT组和KO组不进行套扎与再灌注,其余操作同模型组。应用离体血管张力测定仪测定主动脉收缩反应性,光学显微镜结合透射电子显微镜评价血管形态学变化,蛋白免疫印迹法检测AT1、MAS、ACE和ACE2蛋白的表达。采用酶联免疫吸附法检测血清中血管紧张素(angiotensin,Ang) Ⅱ和Ang-(1-7)含量。结果:与WT相比,WT-TS组小鼠主动脉对去甲肾上腺素(norepinephrine,NE)反应性降低,损伤明显;ACE蛋白表达水平升高(P<0.01),ACE2蛋白表达水平降低(P<0.05);AT1蛋白表达水平降低,MAS蛋白表达水平升高,ATI/MAS比值降低(P<0.01);血清Ang Ⅱ生成增多,Ang-(1-7)水平降低,Ang Ⅱ/Ang-(1-7)比值升高(P<0.05)。与WT组相比,KO组小鼠主动脉在NE低浓度(<10^(-7)mol/L)时的收缩反应性升高,在NE高浓度(>10^(-7)mol/L)时的收缩反应性反而下降,但血管损伤不明显;主动脉AT1、MAS和ACE蛋白表达均增高(P<0.05),AT1/MAS比值降低;血清Ang Ⅱ水平升高(P<0.05),Ang-(1-7)水平无明显变化。与KO和WT-TS组小鼠相比,KO-TS组小鼠主动脉收缩曲线明显右移,对NE的反应性明显下降(P<0.05);血管损伤程度轻度增加(P<0.01);主动脉AT1和ACE表达水平轻度升高(P<0.05),但MAS表达水平显著升高(P<0.01);血清Ang Ⅱ和Ang-(1-7)水平分别升高和降低,因此Ang Ⅱ/Ang-(1-7)比值增大(P<0.01)。结论:TS后ACE2基因敲除小鼠体内缺失的ACE2蛋白可引起主动脉更严重的收缩低反应性,其机制可能与肾素-血管紧张素系统失衡程度增加有关。

国人ACE基因插入/缺失多态性分析及与血清ACE水平的相关性

目的：调查中国人血管紧张素转换酶（ＡＣＥ）基因的插入／缺失多态性分布与及血清ＡＣＥ水平的相关性。方法：采用多聚酶链反应方法测定了６３例健康中国人ＡＣＥ基因型，同时采用微量比色法测定其血清ＡＣＥ水平。结果：中国人中ＡＣＥ基因ＤＤ型占２０．６％，ＤＩ型占４６．１％，Ｉ型占３３．３％，Ｄ与Ｉ等位基因出现频率分别为０．４４和０．５６。ＡＣＥ基因多态性与血清ＡＣＥ水平密切相关，插入／缺失多态性可解释５５％的血清ＡＣＥ总变异。结论：ＤＤ型ＡＣＥ基因可能通过影响ＡＣＥ水平而导致冠心病发病，为临床ＡＣＥ抑制剂应用提供新依据。

冠心病血瘀证与血管紧张素转换酶基因多态性的相关性研究

目的探讨血管紧张素转换酶 (angiotensinconvertingenzyme ,ACE)基因插入 /缺失 (insertion/deletion ,I/D)多态性与冠心病血瘀证的关系。方法用PCR法检测 4 8例血瘀证和 5 2例非血瘀证冠心病患者及 5 4名健康人的ACE基因型 ,同时检测内皮素 (endothelins ,ET)、血管紧张素Ⅱ (angiotensinⅡ ,AgⅡ )、一氧化氮 (nitrogenmonoxide ,NO)值。 结果冠心病血瘀证组ACEDD基因型及D等位基因频率高于非血瘀证组和健康对照组 (P <0 0 1)。ET/NO冠心病血瘀证组明显升高 ,与健康对照组比较差异有显著性(P <0 0 1)。ET、AgⅡ冠心病血瘀证组明显高于非血瘀证组和健康对照组 (P <0 0 5 ,P <0 0 1)。ET/NO、AgⅡ各组DD型均高于II型和ID型 ,其中以冠心病血瘀证组DD型为最高 ,与其他两组比较AgⅡ差异有显著性 (P <0 0 5 ,P <0 0 1) ,与健康对照组比较ET/NO差异有显著性 (P <0 0 1)。