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.

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.

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.

Study of Angiotensin Converting Enzyme Gene Polymorphism in Egyptian Type 2 Diabetes Mellitus with Diabetic Kidney Disease

Objective: Diabetic kidney disease DKD (Diabetic nephropathy DN) is considered one of the chronic micro vascular complications of diabetes mellitus and considered the commonest cause leading to chronic renal failure and chronic renal dialysis. Genetic susceptibility has been implicated in DKD. The angiotensin converting enzyme (ACE) is one of the key roles in the renin angiotensin system cascade by converting angiotensin I to angiotensin II which plays a key role in regulation of blood pressure as well as electrolytes and fluid balance. This study addressed the association of (ACE) gene polymorphisms with DN in Egyptian (T2DM) patients. Methods: Our research comprised of 75 cases of T2DM with diabetic kidney disease, 100 cases of T2DM without DKD and 94 healthy volunteers. Different genotypes of ACE gene were determined by SSP-PCR analysis. Results: Gene polymorphism of ACE (DD, ID, II) in diabetic patient with DKD is 44%, 52%, 4% respectively and for T2DM individuals without DKD is 23%, 72%, 5% respectively. (DD) had significant higher frequencies in T2DM patients with DKD compared to those without DKD (p < 0.005) and (ID) had significant higher frequencies in T2DM without DKD (p < 0.0001). These results indicated that there is an association between ACE gene polymorphisms and susceptibility of diabetic patients to be affected by diabetic kidney disease. Conclusion: From our results, we can conclude that genotype of ACE in Egypt DD is the genotype of cases diabetic kidney disease. So the presence of D allele has a significant relation with diabetic kidney disease. Our data confirm the role of ACE in its relationship with diabetic kidney disease in Egyptian type 2 diabetic patients.

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.

Correlation of SOD-Mn gene polymorphism with renal function and oxidative injury in patients with diabetic nephropathy

Objective:To study the correlation of SOD-Mn gene polymorphism with renal function and oxidative injury in patients with diabetic nephropathy.Methods: Patients who were diagnosed with diabetic nephropathy in Yingshan County People's Hospital between March 2014 and March 2017 were chosen as DN group, and healthy volunteers who received physical examination during the same period were selected as the control group. The SOD-Mn gene rs4880 locus polymorphism and oxidative stress molecule expression in peripheral blood as well as the contents of renal function indexes and oxidative stress indexes in serum were determined.Results: The constituent ratio of SOD-Mn gene CC genotype in DN group was lower than that in control group whereas the constituent ratio of CT+TT genotype was higher than that in control group;serum T-AOC contents as well as peripheral blood Nrf2 and SIRT1 expression intensity of DN group of patients with CC genotype and CT+TT genotype were significantly lower than those of control group whereas serum Scr, BUN, CysC,β2-MG, MDA, AOPP, 8-OHdG and 8-Iso-PGF2α contents as well as peripheral blood NOX4, NOX5, p38MAPK and NF-κB expression intensity were significantly higher than those of control group, and serum T-AOC content as well as peripheral blood Nrf2 and SIRT1 expression intensity of patients with CT+TT genotype was significantly lower than those of patients with CC genotype whereas serum Scr, BUN, CysC,β2-MG, MDA, AOPP, 8-OHdG and 8-Iso-PGF2α contents as well as peripheral blood NOX4, NOX5, p38MAPK and NF-κB expression intensity were significantly higher than those of patients with CC genotype. Conclusion: The mutation from SOD-Mn gene rs4880 locus C to T can aggravate the renal function injury and oxidative stress response in patients with diabetic nephropathy.

Association of Interleukin-6-174G/C Polymorphism with the Risk of Diabetic Nephropathy in Type 2 Diabetes:A Meta-analysis

Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with the clinico-pathological manifestations in immunoglobulin A nephropathy patients

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.

Renoprotective Effect of Benazepril on Diabetic Nephropathy Mediated by P42/44MAPK

The effects of benazepril on P42/44MAPK, angiotensin Ⅱ expression in renal tissue and renal pathological change of the experimental diabetic rats were assessed and the possible mechanism of benazepril's renoprotective effect was explored. Adult male Wistar rats, 11—12 weeks age, weighing initially 160 to 200 g were randomly allocated into 2 groups: control group (A, n=6) and experimental group (n=12). Diabetic rats in experimental group were rendered diabetic by intraperitoneal injection of Streptozotocin (60 mg/kg body weight), and randomly subdivided into B group (diabetic control) and C group (diabetic rats treated with benazepril, 6 mg/kg every day). Studies were performed 8 weeks after induction of diabetes. Twenty-four h urine of every rat was collected to detect urine creatinine. Serum glucose concentration and serum creatinine were determined by collecting blood samples from the inferior vena cava. Body and kidney weight were recorded. Creatinine clearance (Ccr) and ratio of kidney weight to body weight were calculated. Plasma and renal tissue angiotensin Ⅱ concentration was assayed by radioimmunoassay (RIA). The phospo-p44/42MAPK protein expression was detected by Western-blot. The results showed that benazepril had no significant effect on the blood glucose level in diabetic rats in two experimental groups. Ccr and ratio of kidney weight to body weight were increased in group B (P<0.01) as compared with normal rats at the end of the 8th week. At the end of the 8th week, Ccr in group C was lower than that in group B (P<0.01). The ratio of kidney weight to body weight in group C was lower than that in group B at the 8th week. There were glomeruli hypertrophy and slight or moderate mesangium proliferation in diabetic rats, while there was fragmentally proliferative mesangium in group C at the end of the 8th week. Renal tissue angiotensin Ⅱ concentration was significantly increased in group B, while benazepril could significantly decrease the concentration of angiotensin Ⅱ in renal tissue. The expression of the phospo-p44/42MAPK protein in group B was increased as compared with group A, while it was decreased in group C as compared with group B. P42/44MAPK pathway participated in the pathogenesis of diabetic nephropathy. Benazepril can eliminate high filtration of glomeruli, decrease proteinuria, and eliminate renal hypertrophy as well as renal destruction. Renoprotective effect of benazepril in diabetic rats may be partly related to the inhibition of angiotensin Ⅱ-P42/44MAPK pathway.

Effects of adding tripterygium glycosides to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on albuminuria in patients with diabetic nephropathy

Introduction::Tripterygium glycosides (TGs) have been widely used in China to treat diabetic nephropathy (DN);however, proof of their use is scarce. The present study aimed to evaluate the effectiveness and safety of adding TGs to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).Methods::By searching Embase, MEDLINE, Cochrane Library, SINOMED, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases, we identified previous studies that met the specific selection criteria and included them in the meta-analysis. Analyses were performed using Review Manager (version 5.3).Results::Nine randomized controlled trials were included in the final meta-analysis. Patients were compared before and after treatment with ACE inhibitors or ARBs plus TGs, or ACE inhibitors or ARBs alone. The results revealed that treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in 24-h urinary total protein (UTP) levels (trial duration <2 months, mean difference [MD]: -0.25;95% confidence interval [ CI]: -0.32, -0.18;trial duration between 2 and 6 months, MD: -0.39;95% CI: -0.44, -0.33;trial duration >6 months, MD: -2.09;95% CI: -2.89, -1.29) compared with treatment using ACE inhibitors or ARBs alone. Additionally, ACE inhibitors or ARBs plus TGs showed better results after longterm administration. Treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in serum creatinine (SCr) compared with ACE inhibitors or ARBs alone (MD: -9.87;95% CI: -13.76, -5.97). Conclusion::In patients with DN, adding TGs to ACE inhibitors or ARBs significantly lowered both the 24-h UTP and SCr levels. Therefore, ACE inhibitors or ARBs plus TGs might improve the treatment of DN in patients.

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.

Correlativity between blood measures related to blood stasis blocking collaterals and gene expression of angiotensin-converting enzyme of renal cortex in diabetic rats and effect of stasis removing and collaterals dredging

OBJECTIVE: To investigate the correlativity between the changes of blood measures related to blood stasis blocking collaterals and gene expression levels of angiotensin-converting enzyme(ACE)and ACE2 ofrenal cortex in diabetic rats with stasis blocking collaterals syndrome, as well as the effectof stasis removing and collaterals dredging.METHODS: Male Sprague-Dawley rats were divided randomly into normal control group(C group),high-carbohydrate-fat control group(H group) and streptozotocin(STZ)-injecting group. The diabeticrats were induced from rats in the STZ-injecting groupby high-carbohydrate-fat diet combined with STZ intraperitoneal injection, with sustained high-carbohydrate-fat diet fed afterwards, and were further divided into model group(M group)and Chinese medicine of stasis removing and collaterals dredging group(Z group). Rats in the Z group were fed with stasis-removing-and-collaterals-dredging herbal granule suspension intragastrically daily for 16 weeks, while drinking water of corresponding volume was administrated to the rats in other groups. At the end of the 16 th week after successful establishment of models, the ultrastructures of glomeruli in different groups were detected by a transmission electron microscopy; and blood measures related to blood stasis blocking collaterals, including lipid profile and blood viscosity measures, were tested, as well as the relative gene expressions of ACE and ACE2.RESULTS: Changes in ultrastructures of glomeruli in the M group were characterized by lack of clarity in structure and occasional thickening of glomerular basement membrane and extensive fusion in foot processes. The correlation analysis showed that there were positive correlations between lipid profile, blood viscosity, and the ACE mRNA expression levels in the M group(P<0.05), except for cholesterol. And except for triglyceride, the blood measures were in negative correlation with the ACE2 mRNA expression levels in the M group(P<0.05).Compared with the C and H groups, the lipid profile, plasma viscosity and blood viscosity were significantly higher(P<0.01). All the above-mentioned measures were significantly improved in the Z group rats(P<0.05). ACE mRNA expression was significantly higher in the M group thanin the C group(P<0.05). ACE2 mRNA level was significantly lower in the M group than in the C and H groups(P<0.01)and its levelin the Z group was higher than that in the M group(P<0.01).CONCLUSION: Blood measuresrelated to blood stasis blocking collaterals had positive linear correlations with ACE mRNAexpression and negative linear correlations with ACE2 mRNA expression in the M group. Chinese recipe of stasis removing and collaterals dredging could play a renal protecting role for diabetic rats by reducing lipid profile and blood viscosity, down-regulating ACE mRNA expression and up-regulating ACE2 mRNA expression.

Relationship between insertion/deletion polymorphism of angiotensin converting enzyme gene and type 2 diabetic kidney disease

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.

Association of Chinese Medicine Constitution Susceptibility to Diabetic Nephropathy and Transforming Growth Factor-β1(T869C)Gene Polymorphism

Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP） was screened for 180 DN cases and 180 type 2 diabetic mellitus（T2DM） cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire （CCMQ）.Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1（T869C） gene polymorphisms.Results：The DN group has a higher frequency of TGF-β1（T869C） gene polymorphism than the T2DM group,and CC/CT genotypes than the T2DM group[CC,CT,TT（DN group）：88,87,5（cases） versus（T2DM group） 71,73,36（cases）,P0.05].The phlegm-dampness constitution,damp-heat constitution,and blood stasis constitution have correlations with TGF-β1 （T869C） gene polymorphism.Conclusion：Chinese medicine constitutions were associated with TGF-β1（T869C） gene polymorphism,a potential predictor of susceptibility to DN in T2DM patients.

Network Meta-analysis of Four Chinese Patent Medicines Combined with Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Early Diabetic Nephropathy Treatment

The objective of the study is to systematically evaluate the efficacy of four Chinese patent medicines in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in the treatment of early diabetic nephropathy (DN). Retrospectively, previously published randomized controlled trials (RCTs) of four different Chinese patent medicines combined with ACEI or ARB in the treatment of patients with early DN were searched overall from databases. The data were analyzed by R, Generate Mixed Treatment Comparisons and STATA softwares. A total of 78 RCTs were finally included. Network meta-analysis showed that the total effective rate of the Jinshuibao capsule-ACEI/ARB combination group and Huangkui capsule-ACEI/ARB combination groups were better than the others;Jinshuibao capsule-ACEI/ARB combination group reduced the 24-h urinary protein excretion (24-h UTP), urine microalbumin excretion rate (UAER), serum creatinine (Scr), and glycosylated hemoglobin (HbAlc) values. The Huangkui capsule-ACEI/ARB combination demonstrated a better reduction of (blood urea nitrogen [BUN]). Reduced incidences of adverse effects were only observed on treatment with Bailing capsule-ACEI/ARB combination. In early DN, combination of Jinshuibao capsule-ACEI/ARB provided the highest effective rate;moreover, it could reduce the24-h values of UTP, UAER, Scr, and HbAlc;Huangkuai capsule-ACI/ARB combination group showed a good effect on reducing BUN. Bailing capsule-ACEI/ARB combination group had reduced the incidences of adverse reactions.

EDN1基因遗传多态性与糖尿病肾病的相关性研究

目的 探讨EDN1基因的遗传多态性对汉族2型糖尿病肾病发生的影响。方法 选取2020年1月至12月就诊华北石油管理局总医院汉族2型糖尿病患者120例,包括60例2型糖尿病肾病患者和60例性别、年龄相匹配的未患糖尿病肾病的2型糖尿病患者。通过聚合酶链反应(PCR)技术检测EDN1 rs5370基因位点的多态性。结果 糖尿病肾病组血清总胆固醇、三酰甘油、低密度脂蛋白、血清尿素氮、血清肌酐和血清尿酸显著高于非糖尿病肾病组(P<0.05)。EDN1基因的rs5370等位基因在糖尿病肾病组与非糖尿病肾病组间分布存在显著差异。携带T/T基因型的个体相比于携带G/G基因型的个体,糖尿病肾病的发生风险显著降低[OR=0.357, 95%CI(0.132、0.963),P=0.042]。此外,携带等位基因T的个体相比于携带等位基因G的个体,其糖尿病肾病的风险也显著降低[OR=0.565,95%CI(0.339、0.942),P=0.029]。结论 EDN1基因的rs5370多态性可能与2型糖尿病肾病的发生风险相关,T等位基因可能对糖尿病肾病发生具有保护作用。

内皮型一氧化氮合酶G894T基因多态性与2型糖尿病肾病关系的Meta分析

目的系统性评价内皮型一氧化氮合酶(endothelial nitric oxidesynthase,eNOS)中G894T基因多态性与2型糖尿病肾病(type 2 diabetic nephropathy,T2DN)的关联。方法计算机检索PubMed、Cochrane Library、EMBASE、Science Citation Index、Wiley Online Library、Google Scholar、中国期刊全文数据库、中国生物医学文献数据、万方数据库、中国科技期刊数据库等电子数据库,根据纳入与排除标准,纳入G894T基因多态性与T2DN关联的病例对照研究,利用Review Manager5.1和Stata12.0软件,对相关基因型与等位基因频率的差异行Meta分析。结果此次研究纳入23篇文献,共包含T2DN患者4655例与2型糖尿病(type 2 diabetes mellitus,T2DM)患者4093例。①T2DN组基因型TT频率(OR=1.39,95%CI:1.10~1.76,P<0.01)与基因型GT频率(OR=1.33,95%CI:1.13~1.57,P<0.01)均明显高于T2DM组,基因型GG频率明显低于T2DM组(OR=0.66,95%CI:0.55~0.79,P<0.01),结果均存在明显异质性。②等位基因T的频率T2DN组明显高于T2DM组(OR=1.41,95%CI:1.21~1.65,P<0.01)。③中国人群T2DN组基因型GT频率(OR=2.37,95%CI:1.81~3.09,P<0.01)与等位基因T频率(OR=2.07,95%CI:1.62~2.65,P<0.01)均明显高于T2DM组,基因型GG频率明显低于T2DM组(OR=0.42,95%CI:0.32~0.55,P<0.01),且结果均无统计学异质性。④2项研究中的对照组不符合Hardy-Weinberg平衡,剔除该2项研究后行敏感性分析,结果无明显变化。结论G894T基因多态性可能与T2DN的发病相关。

肾虚型DN与ACE基因多态性相关研究

目的 :探讨肾虚型糖尿病肾病 (diabeticnephropathyDN)与肾素血管紧张素Ⅰ转移酶(AngiotensinI convertingenzymeACE)基因多态性的相关性。方法 :分析 2 4 0例 2型糖尿病 (noninsu lin dependentdiabetesmellitusNIDDM)患者中医证型 ,并用PCR方法检测ACE基因型。结果 :肾虚患者ACEDD型的频率和D等位基因的携带率明显增高 ,而ACEⅡ型基因的频率和Ⅰ等位基因的携带率显著降低 (P <0 0 1和P <0 0 5 ) ;且肾阳虚证DD型频率与D等位基因携带率明显高于肾阳虚证 (P <0 0 5 )。结论 :ACE基因不同基因型与DN肾虚关系密切 。