AGT基因M235T多态同哈萨克族高血压病的关联分析

目的探讨新疆哈萨克族血管紧张素原（angiotensinogen,AGT）基因第二外显子（M235T）多态性同高血压病（essential hypertension,EH）的关系。方法4次高血压流行病学调查采集新疆巴里坤哈萨克族EH组278例,正常血压（norm altensive,NT）组220例。测定EH患者和NT者体质量指数（BM I）、空腹血糖、血浆胆固醇、甘油三酯。用MS-PCR法（mutagen ically separated polym erase chain reaction techn ique）检测AGT基因M235T多态性。结果M235T多态性符合Hardy-W e inberg平衡。MT、TT、MM基因型分布频率在EH组及NT组分别为32.7%,62.6%,4.7%;38.2%,51.8%,10.0%。T等位基因频率分别为79.0%及70.9%。M235T基因型频率（P<0.05）及等位基因频率（P<0.01）分布在EH组及NT组均有显著性差异。T等位基因携带者OR值为非T等位基因携带者OR值的2.3倍（95%C I 1.14.6;P<0.05）。对未治疗的EH者在不同基因型间进行比较,未发现MT、MM、TT基因型间收缩压、舒张压、体质量指数、血糖、血脂水平有显著性差异。结论AGT基因M235T可能同新疆哈萨克族高血压病发病相关。     

血管紧张素原基因M235T变异与HBV感染后肝硬化形成的关系

目的: 探讨血管紧张素原(angiotensinogen,AGT)基因M235T分子变异与肝硬化的关系.方法: 提取肝硬化患者和正常人白细胞基因组DNA, 通过PCR、限制性片段长度多态性和测序等技术, 观察在正常组和肝硬化组的不同基因型的分布和等位基因频率的差异.结果: AGT基因 M235T 位点MM、MT和TT基因型的分布在肝硬化组和正常组分别为: 7.8%、40.6%、51.6%与8.0%、59.7%、32.3%, 两组之间不存在差异(χ2=5.120,P>0.05).结论: AGT基因M235T变异可能与肝硬化没有显著关系.     

血管紧张素原基因多态性与慢性心力衰竭的相关性研究

目的探讨血管紧张素原基因(AGT)多态性与慢性心力衰竭(CHF)发病的关系。方法应用聚合酶链反应-限制性片段长度多态性技术检测2004年4月至2005年12月珠海市3家医院的111例CHF患者和110名健康对照者的AGT基因M235T多态性并进行统计学比较。结果共检测出3种AGT基因型,分别为MM型、MT型和TT型。CHF患者TT基因型频率高于对照组,在老年病例与对照组间,差异具有统计学意义(P=0.042)。与非TT型者相比,老年TT型者发生CHF的相对风险率为3.367。结论AGT基因M235T多态性与CHF的发生相关,TT基因型可能是该地区老年人群CHF发病的遗传危险因素。     

血管紧张素原基因M235T和T174M多态性与新疆哈萨克族高血压左室肥厚的关系

目的:探讨新疆哈萨克族原发性高血压(EH)人群中血管紧张素原(AGT)基因M235T和T174M多态性的分布及其与EH伴左室肥厚(LVH)的关系。方法:对86例心电图诊断的EH伴LVH患者(LVH组)与95例不伴LVH患者(NLVH组)进行病例-对照研究,即记录标准12导联以传统的电压诊断标准与Romhilt计分系统积分作为诊断LVH的指标。采用聚合酶链式反应(PCR)与限制性片段长度多态性(RFLP)技术检测AGT基因M235T变异及T174M变异。结果:①M235T基因型有2种形式,T174M基因型有3种形式;2组AGT基因型的分布均符合Hardy-Weinberg平衡;②AGT基因M235T和T174M基因型及等位基因在LVH组与NLVH组的分布均差异无统计学意义(均P>0·05);③按性别分层,M235T基因型和等位基因频率在2组男女之间均差异无统计学意义(均P>0·05);T174M基因型和等位基因频率在LVH组男女之间亦均差异无统计学意义(均P>0·05),而在NLVH组男女之间差异有统计学意义(均P<0·05);④AGT基因M235T,T174M位点不同组合基因型在2组人群的构成不存在显著性差异(P>0·05)。结论:AGT基因M235T及T174M多态性与新疆哈萨克族EH伴LVH的发生无相关性。AGT基因M235T及T174M多态性可能不是新疆哈萨克族EH伴LVH的遗传危险因素。     

血管紧张素原基因M235T多态性与胃癌的相关性

目的 探讨血管紧张素原(AGT)基因M235T多态性与中国人群胃癌易感性的关系.方法 采用聚合酶链反应-限制性片段长度多态性方法检测168例胃癌组和211例健康对照组AGT基因M235T多态性.结果 胃癌组与对照组AGT基因M235T基因型和等位基因分布差异不显著(P＞0.05).根据临床病理特征进行分层分析,发现低分化胃癌患者中TT基因型频率明显高于高中分化胃癌患者(P=0.021)；AGT M235T多态性与胃癌临床分期及转移状态之间无显著差异(P＞0.05).结论 ACT M235T多态性与中国人群胃癌分化程度等临床病理特征密切相关.     

海南汉、黎族人群血管紧张素原基因T174M、M235T的多态性分布

目的 了解海南地区汉族、黎族正常人群血管紧张素原(AGT)基因T174M和M235T的多态性分布情况.方法　应用等位基因特异性PCR技术,对193例海南地区汉族正常人与162例黎族正常人进行AGT基因T174M、M235T多态位点的检测,统计各组基因型频率及各组等位基因频率.结果 M235T基因多态性在海南地区汉黎族正常人间有显著性差异(x~2=10.258,P＜0.01);而T174M基因多态性及其等位基因型频率、M235T等位基因型频率均无显著性差异(x~2=4.062,P>0.1;x~2=1.764,P>0.05;x~2=1.759,P>0.05).结论 海南地区汉族、黎族正常人群M235T基因多态性存在差异,而T174M基因多态性及其等位基因型频率及M235T等位基因型频率的分布相接近.     

AGT基因型对贝那普利降压疗效的影响

目的研究原发性高血压(EH)患者的血管紧张素原(AGT)基因M235T多态性与贝那普利降压疗效的相关性。方法251例EH患者口服贝那普利10～20mg/d,进行为期6周的降压治疗。用聚合酶链反应(PCR)和限制性酶切方法检测所有患者的AGT基因M235T多态性,按MM、MT和TT三种基因型分组。治疗前后及治疗过程中对患者的收缩压(SBP)和舒张压(DBP)等进行监测,以比较不同基因型患者之间的降压疗效。结果基因型为MM、MT及TT者分别为23例(9.2%)、104例(41.4%)和124例(49.4%);在251例患者中,MM、MT及TT三组患者间治疗后SBP和DBP的降幅差异无统计学意义(P>0.05);按年龄分层进行的亚组分析显示:在≥60岁的老年亚组中,治疗后MM、MT及TT三组患者DBP的降幅分别为(14.8±4.8)mmHg,(7.9±7.7)mmHg和(9.8±6.4)mmHg(P=0.034),MM较MT和TT组的DBP降幅大。结论本研究显示,老年(≥60岁)EH患者的AGTM235T多态性与贝那普利降压疗效相关,提示特定的基因多态性可能会影响某些降压药物的疗效。     

血管紧张素原基因两个多态位点与海南地区汉族脑梗死的关系

目的 了解血管紧张素原(AGT)基因T174M和M235T的多态性与海南地区汉族脑梗死的关系.方法 应用等位基因特异性PCR技术,对334例海南地区汉族脑梗死患者和193例海南地区汉族正常对照组中AGT基因T174M、M235T多态位点进行检测,统计各组基因型频率及各组等位基因频率.结果 T174M基因多态性和M235T基因的T等位基因频率增高在脑梗死组与正常对照组间有显著性差异(χ2=6.608,P＜0.05;χ2=4.314,P＜0.05);而M235T基因多态性和T174M基因的T等位基因频率在两组间无显著性差异(χ2=44.080,P>0.1;χ2=3.873,P>0.05).结论 AGT基因T174M多态性及M235T基因的T等位基因频率增高与海南汉族脑梗死发病相关,而M235T基因多态性及T174M基因的T等位基因频率与脑梗死无关.     

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.     

新疆哈萨克族原发性高血压患者内皮型一氧化氮合酶基因G894T多态性研究

目的探讨哈萨克族人群内皮型一氧化氮合酶(eNOS)基因多态性与原发性高血压关联性.方法应用聚合酶链反应、限制性内切酶方法检测了新疆巴里坤县203例哈萨克族高血压病患者和190例正常人群eNOS基因G894T多态性.结果哈萨克族正常人群及高血压患者的eNOS基因G894T多态GG、GT、TT基因型频率分布分别为0.74,0.24,0.02和0.81,0.18,0.01,G和T等位基因分布频率分别为0.86,0.14和0.90,0.10,符合Hardy-Weinberg平衡.群体相关分析结果表明eNOS基因的G及T等位基因分布在高血压病组(EH)及正常血压组(NT)差异无显著性(x2=3.580,P=0.058);基因型频率之间差异无显著性(x2=4.073,P=0.133).然而男性EH组G等位基因频率(0.90)高于NT组(0.86);T等位基因频率(0.06)低于NT组(0.14).结论eNOS基因G894T多态性可能与新疆巴里坤哈萨克族男性高血压有关.     

家族性原发性高血压与血管紧张素原基因M235T突变关系的研究

目的：探讨血管紧张素原基因Ｍ２３５Ｔ突变与家族性原发性高血压（ＥＨ）的关系。　　方法：应用脱氧核糖核酸（ＤＮＡ）杂交和测序检定方法,对一个典型原发性高血压大家系１００名成员［分直系亲属高血压组（ｎ＝ ４５）、直系亲属正常血压组（ｎ＝ ３８）及非直系亲属正常血压组（ｎ＝ １７）］和正常血压对照家系直系亲属２１ 名（为正常对照组）成员按＜ ３５岁和≥３５岁２个年龄层的Ｍ２３５Ｔ突变进行分析。　　结果：比较４组在＜ ３５ 岁和≥３５ 岁２个年龄层的Ｍ２３５Ｔ分布。表明各年龄层中,４组间Ｍ２３５Ｔ基因型及基因频率分布未见显著不同。　　结论：血管紧张素原基因Ｍ２３５Ｔ突变与该家族性原发性高血压没有显著关联;Ｍ２３５Ｔ突变可能不是该家族性原发性高血压的遗传易感因素。     

血管紧张素原M235T基因多态性对血压影响的研究

目的：研究血管紧张素原基因（ＡＧＴ）第二外显子Ｍ２３５Ｔ等位基因的多态性与高血压之间的关系。方法： 应用多聚酶链反应（ＰＣＲ）结合限制性酶切方法对１０５例健康体检者与１０２例原发性高血压（ＥＨ）患者进行基因突变的检测。结果：（１）ＥＨ患者Ｔ２３５ 等位基因频率（０．４４５）高于对照组（０．３２３）,Ｐ＜ ０．０５。在男性ＥＨ患者与男性对照组中差别更为明显（Ｐ＜ ０．０１）;（２）在有家族史的ＥＨ 患者中,Ｍ２３５Ｔ 突变基因型（ＴＴ型）频率高于正常对照组（４２．１％ ＶＳ１８．８％ ,Ｐ＜０．０５）。结论：（１）ＡＧＴ基因的突变与ＥＨ的发病具有相关性。对男性ＥＨ影响可能更大;（２）在有家族史的高血压患者中, ＡＧＴ２３５的ＴＴ基因型与ＥＨ有关     

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。     

简化的血管紧张素原基因单倍型分析与原发性高血压的关系

目的探讨血管紧张素原(AGT)基因连锁不平衡状态、单倍型及与原发性高血压的关系。方法选取497例病例对照样本,采用。PCR-RFIP法检测AGT基因7个位点多态性,同时用最大期望值(EM)算法进行两位点连锁不平衡和单倍型结构估计。结果A-6G,C 31T,T235M三位点两两存在完全连锁不平衡(D’=1)。用5种多态(A-217G,G-152A,A-20C,T174M和T235M)和7种多态(A-217G,G-152A,A-20C,A-6G,C 31T,T174M)估计单倍型结果相同。病例对照研究发现单倍型H2在病例组中频率高于对照组;单个位点分析未见与高血压关联。结论AGT基因研究中A-6G,C 31T,T235M三种多态可简化为其中一种;H2单倍型可能与控制血压的保护性因素连锁不平衡。     

Angiotensinogen M235T polymorphism and left ventricular indices in treated hypertensive patients with normal coronary arteries.

OBJECTIVE: Hypertension and left ventricular hypertrophy (LVH) are important causes of morbidity and mortality in the population. Angiotensinogen (AGT) M235T polymorphism has been associated with LVH, left ventricular dimensions, coronary artery disease and antihypertensive drug response in previous studies. We examined relationship between AGT M235T polymorphism and echocardiographic left ventricular indices in a Turkish population of treated hypertensive patients with normal coronary arteries. METHODS: In this cross-sectional study a Turkish population of 92 hypertensive patients treated in our outpatient clinic were enrolled. All patients had normal coronary angiographic examinations. Genotypes for AGT M235T were determined from peripheral leukocytes. Left ventricular dimensions, mass and function indices, after adjustment for clinical covariates were analyzed by multiple regression analysis according to genotypes. RESULTS: Genotype frequencies for AGT M235T were MM-24.7%, MT-52.8% and TT-22.5%. Left ventricular end-systolic (LVES) dimensions for AGT M235T MM, MT, TT genotypes were 17.9+/-4.2 mm, 19.4+/-6.2 mm, and 16.4+/-2.9 mm, respectively (p=0.08). Angiotensinogen M235T TT genotype showed a trend towards a lower LVES dimension but results were not statistically significant. Left ventricular ejection fractions for AGT M235T MM, MT, TT subgroups were 61.3+/-15.0%, 59.4+/-14.0%, and 67.8+/-8.5%, respectively (p=0.07). Angiotensinogen M235T TT genotype showed a tendency towards lower left ventricular mass index but results were not statistically significant. None of the AGT M235T genotypes predicted left ventricular dilatation, mass or function in treated hypertensive patients with normal coronary arteries. CONCLUSION: Angiotensinogen M235T polymorphism was not useful to predict left ventricular mass, function, hypertrophy or dilatation in a small population of treated Turkish hypertensive patients with normal coronary arteries.     

Association between angiotensinogen gene M235T polymorphism and mitral valve prolapse syndrome in Taiwan Chinese

BACKGROUND AND AIM OF THE STUDY: It has been reported that patients with mitral valve prolapse syndrome (MVPS) also have a disorder in autonomic or neuroendocrine function which can cause many related symptoms. Although a potential role of the reninangiotensin system in the pathogenesis of MVPS has been addressed, the role of the angiotensinogen (AGT) genetic variant in MVPS has not been studied. Thus, a case-controlled study was performed to investigate the possible relationship between AGT gene polymorphisms and MVPS. METHODS: A total of 100 patients with MVP diagnosed by echocardiography and 100 age- and sex-matched normal control subjects was studied. AGT gene M235T and T174M polymorphisms were identified by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in the distribution of AGT gene M235T genotypes (p <0.001) and allelic frequencies (p <0.001) between MVPS cases and controls. An Odds Ratio (OR) for risk of MVPS associated with M235T TT genotype was 8.55 (95% CI 4.51-16.18). An OR for risk of MVPS associated with the T allele at the M235T locus of the AGT gene was 3.27 (95% CI 2.05-5.22). The T174M polymorphism of AGT gene showed no association with MVPS (p = 0.94). CONCLUSION: These findings suggest that the M235T polymorphism of the AGT gene is associated with MVPS in the Chinese population of Taiwan. The association of the TT genotype with MVPS is more noteworthy than an overall increase in the frequency of the T allele at the M235T locus.     

Association of angiotensinogen M235T and A(-6)G gene polymorphisms with coronary heart disease with independence of essential hypertension: the PROCAGENE study. Prospective Cardiac Gene

OBJECTIVES: We examined the relationship between the angiotensinogen (AGT) gene M235T polymorphism, the variant promoter of the AGT gene A(-6)G and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary heart disease (CHD) in native Gran Canaria Island habitants, who have the highest rates of CHD in Spain. BACKGROUND: Some studies subject that the ACE (I/D) polymorphism could be associated with CHD, while AGT (M235T) has been related to essential hypertension. METHODS: We studied 304 subjects with angiographic evidence of coronary artery disease and a clinical diagnosis of myocardial infarction or unstable angina and 315 age- and gender-matched controls. Blood was drawn and DNA extracted. Angiotensin-converting enzyme (I/D) gene polymorphism was analyzed by polymerase chain reaction (PCR) and AGT gene polymorphisms by restriction fragment length polymorphism-PCR and mutagenically-separated PCR. RESULTS: The ACE (I/D) polymorphism showed no association with CHD, whereas the frequency distribution of AGT (M235T) genotypes among patients and controls (235T: 29.1% and 19.0%; M235T: 48.5% and 50.2%; M235: 22.4% and 30.8%, respectively) was statistically different (p = 0.005) and not related to the presence of essential hypertension. Similar results were observed with the AGT A(-6)G polymorphism. In multiple logistic regression analysis, CHD odds ratio associated with 235T and M235 homozygotes were 1.7 (1.1 to 2.6) and 0.54 (0.36 to 0.82), respectively. CONCLUSIONS: This study shows that genetic variation of the AGT (M235T), but not the ACE (I/D), genotypes contributes to the presence of CHD independently of blood pressure profile in a subset of the Spanish population with a high prevalence of cardiovascular disease.     

Relationship between polymorphisms in the renin-angiotensin system and nephropathy in type 2 diabetic patients

BACKGROUND: Renin Angiotensin system is involved in renal function and its polymorphisms may influence diabetic nephropathy. ID ACE polymorphism modulates ACE level whereas M235T AGT polymorphism is involved in arterial hypertension. The A1166C AT1R polymorphism is involved in arterial hypertension and in diabetic retinopathy.METHODS: Two hundred thirty five type 2 diabetic patients were enrolled in this transversal study. Data were documented for clinical characteristics of the population, HbA(1c), urinary albumin excretion, presence of retinopathy or antihypertensive treatment. Polymorphisms were analyzed by PCR techniques. The patients were divided into 3 groups: group 1, without nephropathy (n=118), group 2, microalbuminuria (n=78), group 3, macroalbuminuria (n=39).RESULTS: Diabetes duration was longer (p<0.001), retinopathy (p<0.001) and antihypertensive treatment (p<0.02) were more frequent in group 3 compared to group 1 and 2. The I/D ACE and M235T AGT polymorphisms were not differently distributed between the three groups. In contrast, the CC genotype of the AT1R polymorphism was overrepresented in group 2 (p=0.021). The presence of the CC AT1R genotype considerably increased the incidence of albuminuria after 10 years of diabetes (AA vs CC p=0.01), particurlarly in men. No effect was seen with I/D ACE and M235T AGT polymorphisms.CONCLUSION: In conclusion, we observed an interaction of A1166C AT1R polymorphism with diabetes in men but not of I/D ACE and M235T AGT polymorphisms.