IgA肾病患者AGTM235T基因多态性分析

目的探讨血管紧张素原（AGT）M235T基因多态性与上海地区IgA肾病（IgAN）遗传易感性及临床病理表现的相关性。方法选取上海地区经肾穿刺病理活检证实为IgAN患者105例和健康对照者120例,采用聚合链式反应一限制性片段长度多态性技术（PCR—RFLP）检测AGTM35T基因多态性,并比较不同基因型患者临床病理表现之间的相关性。结果105例IgAN肾病患者的AGTM235T基因多态性与正常对照相比,基因型分布频率差异无统计学意义;年龄、性别、血压、血清肌酐、24h尿蛋白定量、初始的估算肾小球滤过率（eGFR）值等临床指标与AGTM235T基因型无相关性;病理资料显示AGTM235T各基因型病理表现无相关性。结论AGTM235T基因多态性与IgAN患者无显著相关性。     

血管紧张素原基因M235T多态性与结直肠癌易感性关系的研究

目的探讨血管紧张素原(AGT)基因 M235T多态性与中国人群结直肠癌易感性的关系.方法采用聚合酶链反应-限制性片段长度多态性方法检测结直肠癌组151例患者和健康对照组202例AGT基因M235T多态性.结果结直肠癌组与对照组AGT M235T基因型和等位基因分布差异无统计学意义(P>0.05).根据临床病理特征进行分层分析,发现携带TT基因型个体患低分化结直肠癌的风险比携带 MT/MM基因型高2.50倍(P=0.008,OR=2.50;95%CI,1.26-4.97);未发现AGT M235T多态性与结直肠癌临床分期和转移状态之间存在明显相关性(P>0.05).结论 AGT M235T多态性与中国人群结直肠癌的分化程度等临床病理特征密切相关.     

血管紧张素原基因多态性与血管性认知障碍关系的研究

目的 探讨血管紧张素原(AGT)基因G-6A和M235T多态性与血管性认知障碍(VCI)的关系.方法 采用随机对照研究,聚合酶链反应(PCR)方法检测VCI组(67例)、正常对照组(71例)AGT基因G-6A和M235T多态性.结果 VCI组AGT基因M235TT等位基因频率0.73,TT基因型频率0.52,与对照组(0.68,0.45)比较差异无统计学意义(P0.05),TT基因型对VCI的比数比为0.544(95%CI为0.208～1.424,P0.05).VCI组AGT基因G-6 A等位基因频率0.69,AA基因型频率0.48,与对照组(0.63,0.39)比较差异无统计学意义(P0.05),AA基因型对VCI的比数比为0.602(95%CI为0.252～1.738.P0.05).结论 脑梗死伴血管性认知障碍患者与AGT基因G-6A和M235T多态性无关,AGT基因这两个位点多态性未参与发病.     

血管紧张素原基因T174M和M235T多态性与冠心病的相关性

目的研究血管紧张素原(AGT)基因T174M和M235T多态性与高血压并发冠心病的相关性.方法运用单管双相等位基因专一性扩增(single-tube bi-directional allele specific amplification,SB-ASA)方法,在中国人群中,对115例冠心病合并高血压病人、97例高血压对照者和90例正常对照者进行T174M和M235T基因分型.结果M235T多态C/C、C/T和T/T基因型在冠心病合并高血压组中的分布与正常对照和高血压对照相比差异均有显著性(P＜0.01);C、T等位基因频率与对照组相比差异也有显著性(分别为P＜0.05,P＜0.01).但在冠心病合并高血压组中,M235T的分布差异与冠状动脉粥样硬化病变程度无相关性.结论AGT基因M235T多态性可能是中国高血压病人并发冠心病的一个遗传性危险因素.     

血管紧张素转换酶及血管紧张素原基因多态性与高血压左室肥厚的相关研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性及血管紧张素原(AGT)基因M235T多态性与高血压左室肥厚(LVH)的关系。方法对68例超声心动图诊断的未接受治疗的高血压合并LVH患者与76例高血压非LVH患者进行病例对照研究。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ACE基因I/D多态性及AGT基因M235T变异。以二维引导的M型超声心动图测量并计算左室重量。结果①该组高血压患者ACE与AGT基因型的分布均符合Hardy Weinberg平衡。②ACE基因I/D基因型在LVH组与非LVH组的分布差异有显著性(χ2=6.777,P<0.05)。LVH组DD基因型与D等位基因的频率均高于非LVH组(DD基因型:0.31vs0.13,χ2=6.674,P=0.01;D等位基因:0.54vs0.41,χ2=4.837,P<0.05)。③AGT基因M235T基因型在LVH组与非LVH组的分布差异有显著性(χ2=7.133,P<0.05)。LVH组TT基因型与T235等位基因的频率均高于非LVH组(TT基因型:0.62vs0.40,χ2=7.133,P<0.01;T235等位基因:0.78vs0.65,χ2=5.741,P<0.05)。④联合基因分析显示,LVH组ACE DD+AGT TT基因型频率显著高于非LVH组(0.22vs0.05,χ2=8.839,P<0.01),具有该联合基因型者发生LVH的风险比数比(OR=5.094)明显高于单独具有ACE DD基因型(OR=2.949)或AGT TT基因型(OR=2.477)者。结论ACE     

血管紧张素原基因多态性及血糖水平与动脉硬化性脑梗死的相关性

目的：探讨血管紧张素原（AGT ）基因 T174M、M235T 多态性及血糖水平与动脉硬化性脑梗死的关系。方法采用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法检测 AGT 基因 T174M、M235T 位点基因型的多态性,用全自动生化分析仪测定血糖等生化指标。结果 AGT 基因 T174M 位点携带 TT 基因型者、TM 基因型者 ACI 组 GLU 水平高于健康对照组有统计学差异（P ＜0.05）,两组不同基因型间血糖水平比较差异无统计学意义（P ＞0.05）;M235T 位点 MM、MT、TT 基因型者ACI 组 GLU 水平高于健康对照组比较差异有统计学意义（P ＜0.05）,两组不同基因型间血糖水平比较差异无统计学意义（P ＞0.05）。结论血管紧张素原（AGT）基因 T174M、M235T 多态性及血糖水平与动脉硬化性脑梗死三者之间未发现关联性;高血糖是动脉硬化性脑梗死的发生的危险因素之一。     

血管紧张素原基因M235T多态性与糖尿病慢性肾脏疾病的相关性研究

目的探讨血管紧张素原基因M235T是否影响糖尿病肾病的发生。方法收集收治的糖尿病患者300例,根据尿蛋白尿和尿肌酐的比值(ACR)分为三组:单纯糖尿病组(ACR30 mg/g),微量蛋白尿组(30 mg/gACR300 mg/g),大量蛋白尿组(ACR300 mg/g)。另收集健康体检人群100例作为对照组。检测各组常规指标,采用聚合酶链反应-限制性片断长度多态性技术进行M235T多态性位点多态性检测。结果对照组和单纯糖尿病组、微量蛋白尿组、大量蛋白尿组基因型分布均符合Hardy-Weinberg平衡定律;对照组和糖尿病组M235T基因型分布和等位基因频率无统计学差异(P0.05);单纯糖尿病组、微量蛋白尿组和大量蛋白尿组M235T基因型分布和等位基因频率无统计学差异(P0.05)。结论在本区域人群中,血管紧张素原基因M235T多态性与糖尿病肾病无相关性。     

脑梗死患者AGT、ACE和MTHFR基因多态性的研究

[目的]探讨血管l紧张素原(AGT)、血管紧张素转换酶(ACE)和亚甲基四氢叶酸还原酶(MTHFR)基因多态性与脑梗死的相关性.[方法]应用基因芯片技术联合检测中国南方的114例脑梗死患者和76例正常对照者AGT基因M235T、ACE基因I/D和MTHFR基因C667T多态性位点.[结果]脑梗死组的AGT基因TT型和T等位基因、ACE基因DD型和D等位基因频率均显著高于对照组(χ2=6.370,P=0.012;χ2=5.627,P=0.018;χ2=4.216,P=0.040;χ2=11.916,P=0.001);MTHFR基因TT型和T等位基因在脑梗死组和对照组间无差异(χ2=1.037,P=0.287;χ2=0.779,P=0.377).[结论]AGT和ACE基因多态性可能是中国南方汉族人群脑梗死的遗传危险因素,而MTHFR基因多态性可能与脑梗死无相关性.     

IgA肾病和TGF-β1基因多态性的相关性研究

目的:对TGF-β1的G-800A,C-509T,T869C和G915C多态性位点与IgA肾病及其临床表现之间的相关性进行了分析。方法:纳入119例经肾活检证实为IgA肾病的患者和116例健康正常成人作为对照组。采用多聚酶链式反应-限制片段长度多态性分析和多聚酶链式反应-扩增受阻突变体系方法测定TGF-β1的G-800A,C-509T,T869C和G915C多态性位点的基因型,分析其与IgA肾病发病以及临床表现的相关性。结果:研究对象中G-800A和G 915C这两个位点没有多态性。IgAN患者C-509T位点的等位基因型分布与正常对照具有显著性差异(P<0.05),且IgAN患者TT纯合子的频率显著高于对照组(33%vs20%,P=0.02)。C869T位点等位基因的分布无显著性差异。C-509T和C869T位点等位基因分布和患者临床表现无明显的相关性。结论:TGF-β1基因C-509T位点的T等位基因携带可能与IgA肾病的发病易感性具有相关性。     

中国土家族人群血管紧张素原和血管紧张素转化酶基因多态性与冠心病的关系

目的研究血管紧张素原(AGT)基因M235T分子变异和血管紧张素转化酶(ACE)基因I/D多态性与冠状动脉粥样硬化的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测冠心病(CHD)组137例和健康对照组125例AGT基因多态性,采用聚合酶链反应技术检测CHD组和健康对照组ACE基因I/D多态性。结果 CHD组AGT-TT基因型频率为75.91%,显著高于健康对照组43.20%(P<0.01);ACE-DD基因型频率为35.77%,显著高于健康对照组15.20%(P<0.01)。结论在中国土家族人群中,AGT基因TT基因型和ACE基因DD基因型是CHD发病既相互独立又具有协同作用的危险因子。     

Single Strand Conformation Polymorphism (SSCP) as a quick and reliable method to genotype M235T polymorphism of angiotensinogen gene

OBJECTIVES: Conflicting results on the relationship between M235T polymorphism of angiotensinogen (AGT) gene and diabetic nephropathy are reported in the literature, probably due to the small number of subjects, to different inclusion criteria and the different genotype analysis methods used. The aim of the present study was to set up a fast, cheap and reliable method to allow the genotyping of M235T polymorphism in a large number of subjects. DESIGN AND METHODS: We developed in our laboratory a new specifically designed PCR-SSCP method for M235T genotyping whose specificity was compared with that of Allele Specific PCR (ASPCR) and Mutagenically Separated PCR (MS-PCR). The exact M235T genotype was estabilished by direct sequencing. The new PCR-SSCP method was then used to genotype a population of 1171 hypertensive, normoalbuminuric type II diabetes mellitus patients. The patients were also genotyped for ACE I/D polymorphism. For comparison a group of hypertensive non diabetic patients (n = 88) were also screened. RESULTS: The PCR-SSCP method identified the M235T polymorphism with no misinterpretation at variance with ASPCR and MS-PCR methods that showed a preferential amplification of the T allele. The rare Y248C polymorphism of the AGT gene was also detected by PCR-SSCP. In diabetic hypertensive patients the prevalence of TT genotype was higher than in normotensive healthy controls and equivalent to that found in hypertensive non diabetic patients. CONCLUSIONS: The PCR-SSCP method for detection of M235T polymorphism is a powerful and sensitive tool for rapid, cheap and efficient screening of a large number of samples. The results obtained with this method demonstrate an association of the TT genotype of AGT gene with hypertension, both in diabetic and non diabetic patients.     

Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients.

Genetic variability in the renin-angiotensin system may modify renal responses to injury and disease progression. We examined whether the M235T polymorphism of the angiotensinogen (AGT) gene, the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, and the A1166--> C polymorphism of the angiotensin II type 1 receptor gene may be associated with disease progression in 168 Caucasian patients with IgA nephropathy. All patients had serial measurements of their creatinine clearance, proteinuria, and blood pressure (mean+/-SD) with a follow-up of 6.1+/-4.7 yr. The genotype frequencies for each gene were consistent with Hardy-Weinberg equilibrium, and were similar to those of 100 Caucasian control subjects. We examined two primary outcomes: (a) the rate of deterioration of Ccr, and (b) the maximal level of proteinuria. We found that patients with the AGT MT (n = 79) and TT (n = 29) genotypes had a faster rate of deterioration of Ccr than those with the MM (n = 60) genotype (i.e., median values, -6.6 and -6.2 vs. -3. 0 ml/min/yr, respectively; P = 0.01 by Kruskal-Wallis test). Similarly, patients with AGT MT and TT genotypes had higher maximal values of proteinuria than those with the MM genotype (i.e., median values, 2.5 and 3.5 vs. 2.0 g/d, respectively; P < 0.02 by Kruskal-Wallis test). Neither the ACE insertion/deletion nor angiotensin II type I A1166--> C gene polymorphism was associated with disease progression or proteinuria in univariate analysis. Multivariant analysis, however, detected an interaction between the AGT and ACE gene polymorphisms with the presence of ACE/DD polymorphism adversely affecting disease progression only in patients with the AGT/MM genotype (P = 0.008). Neither of these gene polymorphisms was associated with systemic hypertension. Our results suggest that polymorphisms at the AGT and ACE gene loci are important markers for predicting progression to chronic renal failure in Caucasian patients with IgA nephropathy.     

高血压家系AGT基因与细胞因子关系的研究

目的　研究原发性高血压家系血管紧张素原 (AGT)基因多态性及与细胞因子 (IL 1、IL 6、TNF)的关系。方法　对高血压组 40例和家系对照组 38例用PCR RFLP方法分析血AGT基因型 ,用ELISA方法测定血IL 1、IL 6和TNF浓度。结果　发现AGT2 35TT型在高血压组占 70 % ,在家系对照组占 42 %。血IL 1和TNF浓度在高血压组比家系对照组显著升高 ,在AGT基因2 3 5TT型中比2 35TM型中显著升高。结论　AGT基因M2 35T变异是高血压发病的重要危险因素之一 ,细胞因子IL 1和TNF与高血压发病和AGT基因2 35TT型相关 ,它们在高血压发病中可能起重要的AGT基因调控作用     

Angiotensin-converting enzyme insertion/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuria

Angiotensin-converting enzyme (ACE) gene polymorphism is thought to be a potent risk factor for nephropathy and retinopathy in diabetes. We investigated the association between polyneuropathy and gene polymorphisms of both the ACE insertion/deletion (I/D) and angiotensinogen (AGT) M235T genes in 84 type 2 diabetic patients without macroalbuminuria (21 with polyneuropathy and 63 without). ACE genotype distribution did not differ significantly between patients with and without polyneuropathy, but the frequency of the I allele was significantly higher in those with polyneuropathy than in those without. In contrast, neither the genotype distribution nor the allele frequencies of the AGT gene differed between the two groups. In logistic regression analysis using a D-additive model, the D allele had a protective effect on polyneuropathy (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.88). A D-dominant model hypothesis also gave a significant OR (0.28; 95% CI, 0.09-0.90). ACE I/D polymorphism, but not AGT M235T polymorphism, may affect polyneuropathy development in type 2 diabetes without macroalbuminuria.     

Association between AGT T235 variant and microalbuminuria in Canadian Oji-Cree with type 2 diabetes mellitus.

OBJECTIVE: To assess the association between the common variation in the gene encoding angiotensinogen, AGT, and the presence of microalbuminuria in Canadian Oji-Cree with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We compared the frequencies of the AGT promoter and M235T polymorphisms among three subgroups of adult Oji-Cree: 50 subjects who had type 2 diabetes with microalbuminuria, 6 subjects who had type 2 diabetes without albuminuria and 302 non-diabetic, normotensive subjects. RESULTS: We found the AGT T235 allele was present at a significantly higher frequency, and that T235/T235 homozygotes were significantly more prevalent, among the subjects who had type 2 diabetes with microalbuminuria than among the subjects in the other two groups. CONCLUSIONS: The findings suggest that the AGT T235 allele is a determinant of the nephropathy susceptibility related to type 2 diabetes in these aboriginal Canadians.     

血管紧张素原基因多态与原发性高血压合并脑梗死的相关性

目的：分析中国汉族人群血管紧张素原（AGT）基因M235T多态与原发性高血压合并脑梗死的关系。方法：应用PCR-直接测序法在150例单纯原发性高血压、135例原发性高血压合并脑梗死及150例健康对照者中，对M235T多态进行基因分型和统计分析。结果：单纯原发性高血压组与健康对照组相比，M235T多态的基因型和等位基因分布无显著差异。原发性高血压合并脑梗死组的基因型分布（TT=8，CT=50，CC=77）分别与单纯原发性高血压组（TT=19，CT=65，CC=66，X^2=6．513，P=0．039）和健康对照组（TT=26，CT=60，CC=64，X^2=10．878，P=0．004）相比，均有显著差异。原发性高血压合并脑梗死组的C等位基因频率显著高于健康对照组（0．756 vs 0．627，X^2=10．992，P=0．001）和单纯原发性高血压组（0．756 vs 0．657，X^2=6．662，P=0．010）。结论：中国汉族人群中，AGT基因M235T多态可能是原发性高血压合并脑梗死发病的遗传危险因素。     

中国北方汉族新生儿人群ACE和AGT基因遗传多态性的研究

目的研究血管紧张素转换酶（ACE）插入／缺失（I／D）和血管紧张素原（AGT）基因第2外显子M235T多态性各等位基因及基因型在中国北方汉族新生儿人群中的分布频率,比较其在不同种族间的分布差异。方法分别应用聚合酶链式反应和基因测序方法研究了1538名健康新生儿ACE基因多态性分布情况和804名健康新生儿M235T等位基因的变异。结果①ACEI／D基因型和等位基因频率与桂西壮族、新疆维吾尔族、内蒙古鄂伦春族、印度人和美国人比较存在显著差异（P〈0．01）,与巴基斯坦和台湾人比较无统计学差异;AGT基因型和等位基因频率与桂西壮族、苗族、埃及人及葡萄牙人基因型和等位基因频率比较存在显著差异（P〈0．01）,与云南彝族存在不显著差异,与非裔巴西人比较无统计学差异。②ACE及AGT位点基因型及等位基因分布频率在中国北方汉族新生儿人群中没有性别差异。结论中国北方汉族新生儿人群ACEI／D及AGTM235T多态性分布与不同种族人群中存在差异,但无性别差异。     

Candidate gene polymorphisms and their association with hypertension in Malays

BACKGROUND: Knowledge of candidate gene polymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A single nucleotide variant of the angiotensinogene gene (AGT M235T) and endothelial nitric oxide synthase gene (eNOS G894T) have been associated with hypertension. METHOD: A cross-sectional study consisting of 200 hypertensives and 198 age- and sex-matched controls was conducted. Subjects involved in this study were pure Malay for 3 generations. The AGT M235T and eNOS G894T polymorphisms were determined by PCR-RFLP method. RESULTS: The distribution of M235T genotype in the population was 3.5% for MM, 30.4% for MT and 66.1% for TT. No significant difference was observed in genotype (chi(2)=1.30, p=0.52) and allele (chi(2)=0.87, p=0.35) frequencies among the 2 study group. In contrast, the distribution of genotypes for G894T was 74.1% for GG, 24.6% for GT and 1.3% for TT, respectively. Similarly, no significant difference was observed in genotype (chi(2)=0.94, p=0.33) and allele (chi(2)=0.60, p=0.44) frequencies between both study groups. CONCLUSION: The AGT M235T and eNOS G894T polymorphisms are unlikely to play an important role in the pathogenesis of hypertension in Malays.