基因芯片技术分析老年冠心病患者的易感基因

目的 研究血管紧张素转换酶（ACE）、血管紧张素原（AGT）及内皮型一氧化氮合酶（eNOS）基因多态性与老年人冠心病（CHD）的关系.方法 选择老年CHD患者100例及对照者91例,应用基因芯片技术检测ACE、AGT和eNOS基因多态性,并比较其基因型及等位基因频率。结果 CHD组ACE DD基因型频率（28.0%）与对照组（15.4%）比较，差异有统计学意义（P＜0.05）,ACE基因多态性与老年CHD相关.AGT TT基因型频率（75.0%）与对照组（51.7%）比较，差异有统计学意义（P＜0.01）,AGT基因多态性与老年CHD相关.eNOS TT基因型频率（5.0%）与对照组（0.0%）比较,差异无统计学意义（P＞0.05）。同时携带ACE DD和AGT TT基因型或AGT TT和eNOS TT基因型者与老年CHD呈显著正相关（OR=2.9,P＜0.05,OR=1.1,P＜0.05）。结论 ACE和AGT基因多态性可能是中国老年人CHD的危险因素。     

Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND: Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION: Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.     

The renin-angiotensin system genetic polymorphisms and rheumatic mitral valve disease

BACKGROUND AND AIM OF THE STUDY: Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, angiotensinogen (AGT) gene polymorphism and angiotensin II type 1 receptor (AT1R) polymorphism in relation to rheumatic mitral valve disease were examined in a case-control study to investigate possible relationships between these gene polymorphisms and rheumatic mitral valve disease in patients undergoing mitral valve replacement (MVR). METHODS: A total of 50 patients with rheumatic mitral valve disease and undergoing MVR was compared with 50 normal, and age- and sex-matched control subjects. ACE I/D, AGT gene M235T and AT1R-adenine/cytosine 1166 (A1166C) genotype polymorphisms were identified by polymerase chain reaction (PCR) -based restriction analysis. RESULTS: ACE I/D polymorphism differed significantly between the groups. The control group mostly represented the heterozygote ID allele (74%), while the MVR group showed frequencies of 60% for the homozygote DD and II alleles. MM homozygote frequency was significantly greater in controls, but TT homozygote frequency was significantly greater in the MVR group. AT1R-A1166C genotype polymorphism also differed significantly between groups; the MVR group had 73.7% of the AC heterozygote allele, while controls had 64.4% of the AA and 66.7% of the CC homozygote alleles. CONCLUSION: These results provided evidence of an association between ACE I/D polymorphism, M235T polymorphism and AT1R-A1166C genotype polymorphism and rheumatic mitral valve disease.     

基因芯片技术分析与冠心病的相关基因

目的评估血管紧张素原(angiotensinogen,AGT)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)和载脂蛋白E(apolipoprotein E,ApoE)多态性与冠心病的关系,并分析AGT、eNOS和ApoE基因多态性在冠心病的发生和发展中是否存在协同作用。方法选择冠心病患者133例及对照者154名,用基因芯片技术检测AGT、eNOS和ApoE基因多态性,并对比其基因型及等位基因频率。结果冠心病组AGT TT和eNOS TT基因型频率与对照组相比差异有统计学意义,分别为OR=2．63,P<0．001,OR=8．50,P< 0．05。AGT和eNOS基因多态性与冠心病相关。同时携带AGT TT和eNOS TT基因型者与冠心病密切相关(OR=1．05,P<0．01)。ApoE基因型频率及等位基因频率与对照组相比差异无统计学意义(P>0．05)。结论AGT和eNOS基因多态性可能是中国人冠心病的危险因素,基因芯片技术为研究多种易感基因与冠心病的相关性提供了一项高效、敏感的方法。     

Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes

Diabetic nephropathy is the most frequent cause of end-stage renal failure. One of the crucial factors in a development of renal and cardiovascular complications of diabetes is genetic predisposition. The genes of the renin-angiotensin system are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was the evaluation of a possible role of genetic polymorphisms of some of the RAS system genes in the nephropathy in type 2 diabetes. The study was performed in 117 patients with diabetic nephropathy, compared with 200 healthy subjects as a control group. The following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme gene (ACE), M235T of the angiotensinogen gene (AGT) and A1166C of the angiotensin II type 1 receptor gene (AT1R) were evaluated by polymerase chain reaction (PCR). No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. The results for the AT1R gene polymorphism revealed significant differences in allele and genotype frequencies. The homozygous CC genotype was more frequent in patients with diabetic nephropathy than in control group. Both genotypes with the C allele (AC + CC) were found in 56% of patients compared to 38% in control group. These results suggest increased susceptibility to diabetic nephropathy in individuals carrying the CC genotype. Therefore, the A1166C polymorphism of the AT1R gene could be a potential genetic marker for increased susceptibility to renal complications in type 2 diabetes.     

Analysis of the postulated interaction between the angiotensin II sub-type 1 receptor gene A1166C polymorphism and the insertion/deletion polymorphism of the angiotensin converting enzyme gene on risk of myocardial infarction

A synergistic interaction between the insertion/deletion (I/D) polymorphism within the angiotensin-converting enzyme (ACE) gene and an A/C transversion at nucleotide position 1166 within the angiotensin II sub-type 1 receptor (AT1R) gene on risk of myocardial infarction has been reported. The risk associated with the ACE DD genotype increased with the number of AT1R C alleles present. To investigate this further, ACE I/D and AT1R A1166C genotypes were determined in 541 cases recruited at the time of infarction and 507 population-based controls. There was no difference in either the genotype distribution or allele frequencies between cases and controls for either the ACE polymorphism (P=0.48 and 0.35 respectively) or the AT1R polymorphism (P=0.35 and 0.21 respectively). Odds ratios for risk of MI associated with the ACE DD and AT1R CC genotypes were 1.09 (95% CI, 0.82-1.45) and 1.06 (0.67-1.68) respectively. 3.1% of cases versus 3.6% of controls were homozygous for both the D and C alleles (P=0.71). There was no increase in risk associated with the DD genotype in the presence of either one or two AT1R C alleles in the whole cohorts (OR 0.99, 95% CI 0.65-1.51 and 0.76, 95% CI 0.30-1.88, respectively) nor in sub-groups defined by specific risk factors. In conclusion, no evidence was found to support any interaction between the ACE gene I/D polymorphism and the ATIR gene A1166C transversion in determining the risk of myocardial infarction in the population studied.     

血管紧张素转换酶和血管紧张素Ⅱ受体1A1166C基因多态性与脑出血的关系

目的探讨血管紧张素转换酶（ACE）基因插入/缺失多态性和血管紧张素Ⅱ受体1（AT1R）A1166C基因多态性与脑出血的关系,并分析两者是否有协同致脑出血的效应。方法应用聚合酶链反应及限制性片段长度多态性技术,检测80例脑出血患者（脑出血组）和90名健康对照者（健康对照组）的ACE和AT1R基因型和等位基因,并运用Logistic回归分析不同基因型致脑出血的效应。结果脑出血组ACEDD基因型频率为35.0%,D等位基因频率为51.9%,明显高于健康对照组的15.6%和38.9%,均P〈0.05;AT1RAC基因型频率为32.5%,C等位基因频率为16.2%,明显高于健康对照组的11.1%和5.6%,均P〈0.05;Logistic回归显示,170例入组者中,携带AT1RAC基因型（OR：3.852,95%CI：1.719～8.632;P〈0.01）、ACE基因DD型（OR：2.923;95%CI：1.406～6.079;P〈0.01）及同时携带有AT1RAC基因型和ACEDD基因型（OR：4.250;95%CI：1.479～12.209;P〈0.01）是脑出血的独立危险因素。结论ACE基因插入/缺失多态性和AT1RA1166C基因多态性可能是脑出血发病的独立遗传因素;且两者间具有协同致脑出血的作用。     

血管紧张素转换酶和血管紧张素受体基因多态性与冠心病的关系

目的　探讨深圳地区冠心病 (CAD)与血管紧张素转换酶 (ACE)基因与血管紧张素 的 1型受体 (AT1R)基因多态性的关系。方法　分别采用 PCR及 PCR- Afl II酶切法 ,检测 89例 CAD患者和 14 8例健康对照的 ACE和AT1R基因型。结果　 CAD组与对照组比较 ,ACE DD基因型频率 (2 4 .7%比 8.1% ,P<0 .0 1)及 D型等位基因频率 (4 4 .4 %比 33.4 % ,P<0 .0 5 )均为升高。 CAD组与对照组 AT1R基因型频率分布无显著性差异 (P>0 .0 5 )。携带 AT1R C等位基因的个体患 CAD的风险与其同时携带 ACE DD基因型无关 (P>0 .0 5 )。结论　深圳地区CAD的发生和发展可能与 ACE基因 I/ D多态性有关 ,而与 AT1R基因 A116 6 C多态性无关     

肾素-血管紧张素系统双基因多态性与高血压合并舒张性心力衰竭的关系

目的探讨中国南方部分汉族高血压患者肾素一血管紧张素系统中血管紧张素转换酶（ACE）及血管紧张素原（AGT）双基因多态性与舒张性心力衰竭发病的关系。方法应用聚合酶链反应及限制性片断长度多态性技术,对432例高血压患者的ACE基因插入／缺失（I／D）及AGTM235T多态性进行检测。将其中207例合并舒张性心力衰竭者作为病例组,其余225例心功能正常者作为对照组。结果①病例组DD基因型及D等位基因的频率均高于对照组;②病例组TT基因型及T等位基因的频率与对照组比较差异无统计学意义;③联合分析ACE与ACT基因多态性显示,两组中同时具有DD型ACE基因及TT型AGT基因的频率分别为29．0％及14．9％,前者明显高于后者。结论DD型ACE基因可能是该地区高血压患者舒张性心力衰竭发病的遗传危险因素,ACE和AGT基因在慢性心力衰竭的发生中具有协同作用。     

ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS.

The intrapulmonary renin-angiotensin system via tissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients. In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls. Mortality was increased in the ACE DD genotype compared with the I allele, and the ACE I/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7-19.2) compared with the II genotype. In contrast, the AGT (-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome. In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.     

Renin-angiotensin system genes in chronic glomerulonephritis

Glomerulonephritis is a group of diseases with complex etiology, pathogenesis, morphological features and clinical course. The renin-angiotensin system genes are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was to analyze the association of genetic polymorphisms of these genes with glomerular kidney diseases. The study population consisted of 52 patients with immunological glomerular kidney diseases and 50 hemodialyzed patients with end-stage renal failure with glomerulonephritis as primary disease. The control group consisted of 200 healthy subjects. By means of the polymerase chain reaction (PCR) the following polymorphisms were evaluated: insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme gene (ACE), M235T polymorphism of the angiotensinogen gene (AGT) and A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R). No significant association was found between the ACE allele and genotype frequencies and the disease. The allele frequency of the M235T polymorphism was different from that observed in the control group, but differences in the genotype distribution were not statistically significant. The CC genotype of the AT1R gene polymorphism was significantly more frequent in patients than controls. This suggests an increased susceptibility to renal diseases in individuals carrying the CC genotype. This relationship is not associated with hypertension. Our results suggest that in the Polish population the AT1R gene polymorphism might be associated with increased susceptibility to chronic renal diseases.     

血管紧张素原基因T174M和血管紧张素转换酶基因I/D多态性与急性心肌梗死的相关性

目的探讨中国汉族人群血管紧张素转换酶和血管紧张素原基因型的分布及其与急性心肌梗死的关系。方法应用聚合酶链反应技术,对112例急性心肌梗死患者、128例非冠心病患者血管紧张素转换酶I/D多态性及血管紧张素原T174M多态性进行检测。结果血管紧张素转换酶基因型分布及等位基因频率在病例组及对照组间差异有显著性(P<0.01)。病例组和对照组血管紧张素原基因型及等位基因频率总体分布差异亦有显著性(P<0.05)。联合基因分析显示,急性心肌梗死组血管紧张素转换酶DD基因型 血管紧张素原174MM基因型频率显著高于对照组(P<0.01),具有该联合基因型者发生冠心病的风险比数比(OR=8.467)明显高于单独具有血管紧张素转换酶DD基因型(OR=2.558)或血管紧张素原174MM基因型(OR=6.176)者。结论血管紧张素原T174M基因多态性中M等位基因和血管紧张素转换酶I/D基因多态性基因中的D等位基因是中国汉族人群冠心病发病的危险因素之一。同时具有血管紧张素转换酶DD型及血管紧张素原174MM型发生冠心病的相对风险显著高于单基因血管紧张素转换酶DD型及单基因血管紧张素原174MM型。     

血管紧张素原基因和血管紧张素转换酶基因多态性与高血压

目的　研究中国人群中血管紧张素原 (AGT)基因单核苷酸多态性 (SNP)及血管紧张素转换酶 (ACE)基因插入 /缺失多态与高血压病的关系。方法　在 3 4 5例高血压病患者与 2 0 6名血压正常人中采用PCR RFLP法检测AGT基因A 2 0C ,A 6G和M 2 3 5T的多态性 ,用PCR法检测ACE基因 16内含子Alu片段插入 /缺失多态 ,同时用EM算法进行两位点连锁不平衡分析。结果　在M 2 3 5T和A 2 0C ,M 2 3 5T和A 6G ,A 2 0C和A 6G位点观察到了连锁不平衡 (P <10 - 4)。病例 对照检验显示T2 3 5等位基因频率在高血压组中高于对照组 ,且高血压病患者中ACE (DD +ID) +AGT TT2 3 5基因型频率高于对照组。结论　受检人群中AGT基因各多态频率处于两两连锁不平衡 ,但AGT基因即T2 3 5位点以隐性作用方式与高血压关联 ,T2 3 5等位基因与ACE D等位基因在高血压病发生中具协同作用     

肾素-血管紧张素系统基因多态性与原发性高血压左心室肥厚关系的探讨

目的　探讨肾素 血管紧张素系统 (RAS)基因多态性与原发性高血压左心室肥厚 (EH LVH)的相关性以及在EH LVH产生中的多基因协同作用。方法　对 10 9例原发性高血压病 (EH)患者 ,采用聚合酶链反应 (PCR)以及聚合酶链反应 限制性片段长度多态性方法检测血液白细胞染色体DNA中血管紧张素转换酶 [ACE(I D) ]、血管紧张素原 [AGT(M2 35T) ]和血管紧张素Ⅱ 1型受体 [AT1 R(A116 6C) ]基因多态性 ;利用超声心动图检测左心室质量 (LVM)并计算左心室质量指数 (LVMI)。结果　ACE(I D)基因多态性D等位基因频率在EH LVH组中明显增高 (χ2 =4 .6 9,P=0 .0 30 ) ,男性EH患者中 ,ACE(I D)基因型构成比与LVH有关联 (χ2 =9.5 5 ,P =0 .0 0 8)。协同存在AGT TT型时 ,ACE(I D)基因多态性与EH LVH有关 (χ2 =6 .2 2 ,P =0 .0 4 4 ) ,且D等位基因在EH LVH明显增高 (χ2 =6 .91,P =0 .0 0 9) ,该类EH患者发生LVH的相对危险度增高 (OR :2 .5 0 ,95 %CI:1.2 5～ 5 .0 0 )。结论　ACE(I D)基因多态性D等位基因可能是LVH的独立危险因子。ACE基因多态性与AGT基因多态性之间的协同效应表明 ,同时携带AGT TT型时 ,具有ACE(I D)基因多态性D等位基因的EH患者更易发生LVH。     

The involvement of the renin-angiotensin system gene polymorphisms in coronary heart disease

INTRODUCTION AND OBJECTIVES: Previous studies angiotensin-converting enzyme gene insertion/deletion polymorphism ACE (I/D), angiotensinogen gene polymorphism, and angiotensin II AT1 receptor polymorphism in relation to coronary heart disease controversial results. This study was designed to analyze the association between these gene polymorphisms and the first coronary event in individuals residing on Grand Canary Island, Spain. PATIENTS AND METHOD: Case-control study. Case subjects (n = 304) were recruited at the first coronary event; age-matched controls (n = 315) were randomly selected from the Grand Canary population. Participants were examined for the usual risk factors. Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by PCR and restriction analysis. RESULTS: Neither ACE (I/D) nor AT1 receptor polymorphism was associated with coronary heart disease, whereas the frequency distribution of AGT M235T genotypes among patients and control subjects (TT: 29% and 19%; MT: 48% and 50%; MM: 22% and 31%, respectively) was statistically different (p = 0.003). Multiple logistic regression analysis identified the TT genotype of the angiotensinogen gene (OR = 1.9; 95% CI 1.1-3.4), diabetes (OR = 4.4; 95% CI 2.0-9.4) and hypertension (OR = 2.1; 95% CI 1.3-3.3) as risk factors predicting the coronary event. CONCLUSIONS: Our results provide no evidence of an association between ACE (I/D) or AT1 receptor polymorphism and coronary heart disease. However, homozygosity for the T allele of the angiotensinogen gene, diabetes and hypertension independently place individuals at higher risk of experiencing a coronary event on Grand Canary Island.     

血管紧张素原基因核心启动子区域的单核苷酸多态与冠心病的关系

目的:在中国南方汉族人群中,检测血管紧张素原基因(AGT)5'端核心启动子内AGCE1区域的单 核苷酸多态(SNPs),并探讨其与冠心病发病的关系。方法:应用PCR直接测序技术检测AGCE1区域的序列,并 结合多重SNaPshot反应在145例血压正常的冠心病患者和185例健康对照者中对所检测的SNPs进行基因分 型。结果:在AGT基因AGCE1区域-20和-6位上发现2个SNPs,且A 20C和G 6A多态呈连锁不平衡。A 20C多态的基因型分布在冠心病组(CC=4,AC=29,AA=112)和对照组(2,61,122)之间差异有统计学意义(P <0.05)。C等位基因频率在两组间虽有差异(12.76%/17.57%),但未达到统计学意义(P>0.05)。G 6A多态 的基因型分布和等位基因频率在冠心病组与对照组之间差异均无统计学意义。单倍型分析表明,各组单倍型的 频率分布在两组间差异亦无统计学意义。结论:AGT基因的A 20C多态可能与血压正常人群的冠心病发病相 关。     

The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction.

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.     

血管紧张素转化酶基因插入/缺失多态性与冠心病发病的关系

目的 :探讨血管紧张素转化酶 (ACE)基因多态性与冠心病 (CHD)发病的关系。方法 :以人基因组DNA为模板 ,应用聚合酶链式反应 (PCR)检测 5 0例CHD组和 5 6例正常对照组ACE基因第 16内含子插入 /缺失 (I/D)多态性 ,并按性别分组计算各组基因型和等位基因频率。结果 :①在CHD组中 ,ACE基因DD基因型和D等位基因频率分别为 36 %和 6 0 % ,正常对照组分别为 16 %和 4 1% ,两者相比差异有统计学意义 (P <0 .0 1)。②男性CHD组DD基因型和D等位基因频率均显著高于对照组 (均P <0 .0 5 )。女性CHD组DD基因型频率显著高于对照组 (P <0 .0 1) ,D等位基因频率与对照组比较差异无统计学意义。结论 :CHD与ACE基因I/D多态性有显著相关性 ,不论男性和女性 ,ACE基因DD基因型均可能是CHD发生发展过程中重要的危险因素之一。     

血管紧张素转换酶基因多态性与冠脉病变严重程度的相关性研究

目的探讨血管紧张素转换酶(ACE)基因I/D多态性与冠心病及冠脉病变严重程度的关系.方法对122例冠心病患者进行冠状动脉造影,判定冠脉病变支数(狭窄程度≥75%)和危险记分.用聚合酶链式反应(PCR)技术检测病例组和80例健康人群ACE基因多态性.结果ACE基因型分布和等位基因频率在病例组和对照组间差异有显著性,病例组DD基因型(38.5%)和D等位基因频率(55%)显著高于对照组(13.7%,41%;P＜0.05).冠脉病变支数和危险记分在ACE基因型间差异无显著性(P＞0.05).结论ACE基因多态性中DD型和D等位基因是冠心病发病的独立危险因素,但与冠脉病变严重程度不相关.     

Peripheral vascular disease in Type 2 diabetic Chinese patients: associations with metabolic indices, concomitant vascular disease and genetic factors.

AIMS: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of vascular disease, but do not explain the lower burden of cardiac and peripheral vascular disease (PVD) in Chinese compared with Caucasians. The role of renin-angiotensin system (RAS) gene polymorphisms and conventional vascular risk factors has not been determined. METHODS: A total of 3097 Chinese diabetic subjects were screened for PVD, which was identified in 194 of the 2967 patients with Type 2 diabetes. Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between the PVD patients and 1046 age, gender and diabetes duration-matched patients without PVD. RESULTS: PVD identified in 6.5% was associated with significantly worse glycaemic control, lipid profile and renal function. Smoking was more common, as were the other macro- and microvascular diseases. The prevalence of hypertension was similar between the groups, yet diastolic blood pressure was slightly lower in the PVD group. The ACE D allele was significantly more frequent in patients with PVD compared with the matched diabetic controls (38.1 vs. 29.8%, P = 0.039). No differences in the AT1R or AGT polymorphisms were observed. CONCLUSIONS: PVD was associated with a worse metabolic profile and greater concomitant vascular disease than controls. The ACE I/D polymorphism was associated with PVD in these Type 2 diabetic patients.