肾素-血管紧张素系统双基因多态性与老年人冠心病慢性心力衰竭的关系

目的:探讨中国南方部分汉族人群的老年冠心病患者中,肾素-血管紧张素系统中的关键成分即血管紧张素转换酶(ACE)及血管紧张素原(AGT)双基因多态性与慢性心力衰竭(心衰)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396例老年冠心病患者的ACE基因插入/缺失(I/D)及AGT基因M235T多态性进行检测.将其中196例合并慢性心衰患者作为病例组,其余200例心功能正常者作为对照组.结果:①病例组DD基因型频率及D等位基因频率均高于对照组;②病例组TT基因型频率及T等位基因频率均高于对照组;③联合分析ACE与AGT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28.6%及15.0%,前者明显高于后者.结论:DD型ACE基因及TT型AGT基因可能是中国南方部分汉族老年冠心病慢性心衰患者发病的遗传危险因素,ACE和AGT基因在慢性心衰的发生中具有协同作用.     

血管紧张素转换酶和血管紧张素原基因多态性与冠心病的关系

目的探讨血管紧张素转换酶（ACE）插入／缺失（I／D）多态性和血管紧张素原（AGT）M235T基因多态性与冠心病（CHD）的关系。方法应用多聚酶链反应结合限制性内切酶法（PCR—RFLP）对110例冠心病患者、62例冠状动脉造影正常者以及18名门诊常规体检无冠心病史者基因多态性进行分析。结果①CHD组ACE基因DD基因型及D等位基因频率明显高于健康对照组（分别为43．6％、60．5％比26．3％、44．4％）,差异有统计学意义‘P〈0．05）。CHD组AGT基因TT基因型及T等位基因频率明显高于对照组（分别为66．4％、78．6％比42．5％、60．6％）,差异有统计学意义（尸〈0．05）。②男性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因TT基因型和T等位基因频率均显著高于对照组（均P〈O．05）。女性CHD组ACE基因DD基因型和D等位基因频率以及AGT基因‘rr基因型和T等位基因频率与对照组比较差异无统计学意义（P〉0．05）。③联合分析ACEDD型及AGTTr型罹患冠心病的相对风险,其比数~L（OR）为4．904,高于单基因ACEDD型（2．175）及AGTTT型（2．669）。结论ACE基因I／D多态性及AGT基因M235T多态性与CHD有显著相关性,同时具有ACEDD型及AGT TT型发生冠心病的相对风险显著高于单基因ACEDD型及单基因AGT‘丌型。性别也可作为冠心病的危险因素。     

不同性别高血压病患者肾素-血管紧张素系统多基因多态性关联研究

目的探讨不同性别高血压病患者与肾素-血管紧张素系统,包括血管紧张素Ⅱ-1型受体(AT1R)基因、血管紧张素转化酶(ACE)和血管紧张素原(AGT)多基因多态性的相关性。方法应用多聚酶链式反应-限制性酶切法(PCR-RFLP)检测95例高血压病患者和98例健康对照者的AT1R基因1166位点、ACE基因I/D以及AGT基因M235T基因型,比较不同性别两组间基因型和等位基因型的分布频率。结果男性高血压组AT1R基因、AC/CC基因型和ACE基因DD基因型频率高于对照组,1166C和D等位基因频率明显高于对照组;AGT基因TT基因型及T等位基因频率较对照组为高,但差异无统计学意义;在女性,ACE基因D等位基因频率较其对照组为高(P0.05),余各基因型和等位基因频率在病例组与对照组之间均未见差异。结论肾素-血管紧张素系统多个基因位点变异与男性高血压病发病有关,只有较少基因位点多态性参与女性发病。     

RAS三种不同基因多态性与原发性高血压的相关性

目的 探讨肾素—血管紧张素系统(RAS) 血管紧张素原(AGT)基因T704C多态性、血管紧张素转换酶(ACE)基因I/D多态性及血管紧张素Ⅱ的1型受体(AT1R)基因A1166-C多态性与原发性高血压（EH）的关系.方法 采用PCR及PCR-限制性片段长度多态性(PCR-RFLP)方法,对220例EH患者（EH组）和1 004例非原发性高血压患者（NEH组）ACE基因Alu I/D多态性、AGT基因T704C多态性、AT1R基因A1166-C多态性进行基因型检测,计算等位基因频率.结果 两组AGT基因型及ACE基因型、等位基因频率均有显著差异（P分别 ＜0.01、0.05、0.05）;EH组TC-II、TC-AA、II-AA联合基因型频率显著低于NEH组（P均＜0.05）,CC-ID、CC-DD 、CC-AA、CC-AC+CC联合基因型频率显著高于NEH组(P均 ＜0.01).结论 携带AGT 基因CC基因型、ACE基因D等位基因者可能为发生EH易感人群;TC-II、TC-AA、II-AA联合基因型对EH的发生可能起负协同作用,而CC-ID、CC-DD、CC-AA、CC-AC+CC联合基因型可能起正协同作用.     

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。     

血管紧张素系统基因多态性在IgA肾病高血压型和尿检异常型中的分布

目的：根据临床病理表现将IgA肾病（IgAN）分为7种类型。比较高血压型和轻度尿检异常型临床表现及血管紧张素原（AGT）、血管紧张素转化酶（ACE）、血管紧张素Ⅱ受体（AT1R）基因类型分布的差异，及其对IgAN高血压型患者临床表现的影响。方法：PCR法及PCR—RFLP法检测AGT基因M235T多态性、ACE基因I／D多态性、AT1R基因A1166C多态性。回顾性分析IgAN高血压型与轻度尿检异常型患者及IgAN高血压型不同基因型之间临床病理表现的差别。结果：IgAN高血压型患者起病即表现为明显血压升高，肾功能减退，小管功能损害，病理表现出较多球性硬化、间质纤维化等慢性病变，与尿检异常型相比均有统计学意义。在高血压型患者中AGT基因TT、MT、MM基因型分别占65％、28％、7％，T等位基因频率为79％，与尿检异常型相比差异有统计学意义。ACE基因DD型、DI型、Ⅱ型在高血压型患者中分别为15％、54％、31％，与尿检异常型相比差异也有统计学意义，D等位基因频率为42％，显著高于尿检异常型。AT1R基因中，未检测出CC基因型，两组基因型及基因频率相比均无统计学差异。在高血压型患者中，DD基因型及DD＋TT基因型患者起病时血压明显高于其他基因型患者，病理表现亦较重。结论：IgAN高血压型与尿检异常型患者不仅在临床病理表现上有显著不同，在基因背景上也有一定差异，提示IgAN的分型对诊断和治疗均有重要意义。在高血压型患者中，AGTT等位基因及ACED等位基因与血压升高等较重的临床病理表现有密切关联。     

连锁分析血管紧张素转换酶基因插入/缺失多态性和血管紧张素原 M235T基因多态性与肥厚型心肌病的关系

目的 连锁分析中国人群血管紧张素转换酶（ACE）基因插入／缺失多态性及血管紧张素原（AGT）M235T基因多态性与肥厚型心肌病（HCM）发病的关系。方法 对63例HCM患分别用PCR法检测ACE基因插入／缺失和AGT M235T基因多态性。结果 HCM患中ACE DD＋AGT TT基因型的比数比高于单基因型,其心脏事件发生率高于其他基因型组合和AGT TT型。结论 同时具有ACE DD＋AGT TT基因型,较单基因型发生HCM的风险率显增高;同时具有ACE DD＋AGT TT基因型的HCM患发生心脏事件的危险更大。     

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-血管紧张素系统三个关键基因与2型糖尿病肾病发病关系的研究

目的：了解肾素－血管紧张素系统（RAS）中三个关键基因血这紧张素I转换酶（ACE）,血管紧张素原（AGT）及I型血管紧张素受体（AGTR1）基因的4个多态位点是否与中国人2型糖尿病及其合并的糖尿病肾病（DN）的发生有关联。方法：在173例上海地区中国汉族人中用PCR基因扩增,内切酶消化或同位素标记放射自显影等方法进行基因分析。比较DN组及其亚组和对照组各组间的基因频率,并用logistic回归分析各基因多态位点和其他因素对DN发病风险的影响。结果：DN组的ACE基因等位基因D和DD型频率增高（P分别为0．022和＜0．001）,按病程划分,＜5年及≥5年亚组与DN（－）组比较亦可见等位基因频率差异,但进一步按DD型和非DD型分组,并经连续校正试验发现其阳性主要表现在病程＜5年与DN（－）组比较中,DN组的AGT－M235T多态位点基因型和等位基因频率与未合并DN的糖尿病组比较有显著意义（P分别为0．018和0．004）,表现为等位基因T与TT型增多,且仅表现于病程＜5年亚组,不同病期DN亚组间的基因频率无显著变化。ACE,AGT及AGTR1基因四个多态位点与合并的高血压,冠心病等因素经logistic回归分析后提示ACE基因及AGT－M235T为DN,尤其病程＜5年亚组的发病风险因素,结论：RAS中ACE基因I／D和AGT基因M235T多态位点与2型糖尿病合并的肾病发生相关联,前者的DD型和等位基因D以及后者的TT型和等位基因T可能参与较早起病DN的发病。     

肾素-血管紧张素系统基因多态性与冠心病合并慢性心力衰竭严重程度的关系

目的检测部分中国南方汉族人群冠心病合并慢性心力衰竭患者的ACE及AGT基因多态性分布情况,以探讨肾素-血管紧张素系统（1／AS）基因多态性对冠心病合并慢性心力衰竭严重程度的影响。方法应用聚合酶链反应及限制性片断长度多态性技术,对210例冠心病合并慢性心力衰竭患者的ACE基因插入／缺失（I/D）及AGT基因M235T多态性进行检测,采用彩色多普勒检测患者的左室舒张末内径（LVDD）及左室射血分数（LVEF）。结果不同ACE基因型患者其LVDD及LVEF均存在差异,LVDD（DD）〉LVDD（ID）〉LVDD（II）（P〈0．05）,LVEF（DD）〈IXEF（ID）〈LVEF（II）（P〈0．05）,不同AGT基因型亚组间LVDD及LVEF差别均无统计学意义（P〉0．05）。结论ACE基因I／D多态性与中国南方部分汉族人群冠心病合并慢性心力衰竭的严重程度相关,DD型ACE基因的冠心病患者发生心力衰竭后病情较其他基因型者更加严重。AGT基因M235T多态性似与冠心病合并慢性心力衰竭的严重程度无关。     

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。     

Genetic polymorphisms of angiotensin-I converting enzyme, haptoglobin and angiotensinogen and oxidative stress parameters in 12 to 15-year-old adolescents.

BACKGROUND: Angiotensin-converting enzyme (ACE) I/D, haptoglobin (Hp) 1/2 and angiotensinogen (AGT) M235T gene polymorphisms have been associated with the risk of various cardiovascular conditions. Oxidative stress and reactive oxygen species have also been implicated in endothelial injury. In a randomly selected sample of healthy adolescents, we studied the relationship between these genetic polymorphisms and somatic characteristics, blood pressure and certain biochemical markers of oxidative stress. METHODS: A sample of 49 healthy adolescents were genotyped for ACE I/D, Hp 1/2 and AGT M235T polymorphisms. Anthropometric parameters, blood pressure and lipid profile were evaluated using internationally recommended methods. Serum ACE activity and oxidative stress markers were determined either by spectrophotometric methods or with commercially available kits. RESULTS: Males had higher values for ACE activity than females (p < 0.01). The haptoglobin Hp allele 1 and the ACE D allele were associated with higher ACE activity (p < 0.05 and p < 0.001). ACE activity was similar between AGT genotypes. Higher levels of MDA-LDL/Apo B were observed in individuals with both ACE DD and Hp 2-2 genotypes. Carriers of the AGT TT genotype showed higher diastolic blood pressures than other AGT genotypes. CONCLUSION: Carriers of both ACE DD and Hp 2-2 genotypes have a higher pro-oxidant status and AGT TT carriers have higher diastolic blood pressures, which may indicate a higher risk for development of hypertension in these individuals.     

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.     

Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study

Background

Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies.

Methods

The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used.

Results

No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P =.08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype.

Conclusion

The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with increased risk for hypertension.     

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 M235T polymorphism in the angiotensinogen gene is associated with the risk of malignant hypertension in white patients

BACKGROUND: Malignant hypertension can be considered an extreme phenotype of renin-mediated hypertension. Therefore, we compared the allelic frequencies of the angiotensinogen (AGT) M235T, angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II-type I receptor (AT1R) A1166C polymorphisms in malignant hypertensive patients with hypertensive and normotensive controls. METHODS: A total of 101 consecutive patients between 1995 and 2005 admitted to a large university hospital fulfilled the criteria for malignant hypertension. Seventy-five patients (74%) were compared with 150 hypertensive and 150 normotensive controls, randomly selected from a population study and individually matched on age, sex and ethnicity. RESULTS: The odds of malignant hypertension in white subjects with the TT genotype of the AGT M235T polymorphism was 14.3 (5.5-37) compared to hypertensive controls, and 9.4 (3.8-23.2) compared to normotensive controls. Adjustment for age, sex, smoking and antihypertensive therapy did not affect this association. The association of AGT M235T with malignant hypertension was not significant in blacks. In patients with malignant hypertension, the TT genotype was associated with more severe renal dysfunction and microangiopathic haemolysis. No differences were found in allele frequencies of the ACE I/D or the AT1R A1166C polymorphisms between study groups. CONCLUSIONS: The TT genotype of AGT M235T is associated with malignant hypertension in whites, carriers having an odds of approximately 10 to 1 compared to hypertensive and normotensive controls. These observations may provide a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. Larger association or linkage studies are needed for a more detailed risk assessment.     

Polymorphism in the angiotensin converting enzyme but not in the angiotensinogen gene is associated with hypertension and type 2 diabetes: the Skaraborg Hypertension and diabetes project

OBJECTIVE: To study the association between polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene and hypertension and/or type 2 diabetes in a community population. PATIENTS AND METHODS: The insertion (I)/deletion (D) polymorphism of the ACE gene and the M235T polymorphism of the AGT gene were genotyped in 773 nondiabetic individuals with hypertension, 193 normotensive patients with type 2 diabetes, 243 patients with type 2 diabetes and hypertension, and in 820 normotensive control individuals identified in a community-based study. RESULTS: The DD genotype was associated with hypertension in individuals less than 70 years [odds ratio (OR) = 1.54, confidence interval (CI) = 1.09-2.18] and remained so when patients with type 2 diabetes were excluded from the analysis (OR = 1.45, CI = 1.01-2.09). The strongest association was with the combination of type 2 diabetes and hypertension (OR = 2.19, CI = 1.09-4.38). There was no association with type 2 diabetes without hypertension. No association was observed between the M235T variant or the 3'-microsatellite polymorphism of the AGT gene and hypertension. CONCLUSION: The D-allele of the ACE gene ID polymorphism increases susceptibility to hypertension, particularly when associated with type 2 diabetes. No association was observed between the M235T variant or 3'-microsatellite polymorphism of the AGT gene and hypertension.     

Renin-angiotensin system gene polymorphisms: assessment of the risk of coronary heart disease

BACKGROUND: Renin-angiotensin system genes are candidate genes in cardiovascular system diseases. Angiotensinconverting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene polymorphisms are considered risk factors in coronary heart disease (CHD). AIM: To evaluate the involvement of the ACE, AGT and AT1R genetic variants in predisposition to CHD as well as their association with other known risk factors. METHODS: The study included 400 male subjects (200 with CHD and 200 healthy individuals). Genotypes were determined by a polymerase chain reaction (PCR). For the AGT and AT1R genes a restriction analysis of the PCR product was performed. The allele frequency and genotype distribution were compared between groups. RESULTS: The allele and genotype frequencies of the ACE gene were similar in both groups, however, a significantly higher frequency of the DD genotype was observed in the presence of hyperlipidemia (39% vs 24% in non-hyperlipidemic subjects, p<0.01). The AGT gene polymorphism was associated with the development of CHD. The T allele was significantly more frequent in patients than in the control group (55% vs 44%, p<0.05). The heterozygous MT genotype was observed in 61% of patients compared to 40% in the controls (p<0.05). The A1166C polymorphism of the AT1R gene was also associated with CHD as well as with age at the onset of disease. The frequency of the C allele was 29% compared to 21% in the control group (p<0.01) and the frequency of the CC homozygote was almost three times higher in patients. CONCLUSIONS: There is an association between molecular variants of the angiotensinogen and angiotensin II type 1 receptor and increased risk of CHD. The DD genotype of the ACE gene polymorphism and the TT genotype of the AGT gene polymorphism were significantly more frequent in patients with hyperlipidemia. The TT genotype of the AGT gene M235T polymorphism was associated with an increased risk of CHD and myocardial infarction only in smokers.