原发性高血压侯选基因的相关研究进展

原发性高血压是一复杂的病理生理过程,且影响因素很多,至今对其发病机制仍不完全清楚,但遗传背景是原发性高血压发病的重要原因。近几年该领域研究热点已深入到基因水平,并找到多个原发性高血压侯选基因,本文将研究较为深入的原发性高血压侯选基因作一综述。     

原发性高血压的相关基因研究

原发性高血压的遗传易感性已十分明确,因此我们有必要结合该疾病的分子生物学机制探讨其发生及发展的机理.本文从调控血压的几大系统出发对原发性高血压的相关基因进行了综述.     

原发性高血压相关基因研究进展

原发性高血压（EH）作为一种严重危害人类健康并且发病率呈逐年上升趋势的常见多发的多基因遗传性疾病，其相关基因研究近年来非常活跃。目前大多数研究采用候选基因法和全基因组扫描两种方法寻找与EH相关的基因．并有研究人员已开始进行有关基因功能的研究，本文对其中研究较为深入的EH候选基因研究进展做一综述。     

原发性高血压相关基因多态性的临床分析

目的 研究中国南方汉族人群中血管紧张素原(AGT235)、血管紧张素转换酶(ACEI/D)、心钠素(ANP2238)、C型心钠素受体(NPRC-55)和内皮型一氧化氮合酶(eNOS298)基因多态性与原发性高血压(EH)的关系.方法 选择EH患者81例及对照者120例,采用基因芯片技术检测AGT235、ACEI/D、ANP2238、NPRC-55、eNOS298基因多态性,并比较其基因型及等位基因频率. 结果 EH组AGT235 TT基因型频率(53.1%)与对照组(45.8%)无差异(P>0.05);EH组患者ACEI/D DD基因型频率(48.1%)与对照组(4.2%)差异显著(P<0.001);EH组ANP2238CC基因型频率为6.1%,与对照组(8.3%)无差异(P>0.05);EH组NPRC-55CC基因型频率为65.4%,对照组(68.3%)无差异(P>0.05);EH组eNOS298DD基因型频率为3.7%,与对照组(0.8%)无差异(P>0.05).结论 ACEI/D基因可能是EH的易感基因,AGT235、ANP2238、NPRC-55和eNOS298基因与EH不具有相关性.     

高血压致病相关基因研究进展

原发性高血压是是由遗传因素和环境因素共同作用而引起的多基因遗传性疾病,是导致脑卒中、冠心病、心功能不全、肾脏疾病等的主要因素.目前国内外研究者所涉及到的原发性高血压候选基因近150种,本文就血管紧张素Ⅱ,血管紧张素受体,肾素,激肽,G蛋白信号2调节基因及心钠素等候选基因的研究进展作一综述.     

原发性高血压相关基因研究进展

原发性高血压是一种遗传与环境因素相互作用所致的多基因遗传性疾病 ,其相关基因研究在近年来非常活跃。采用候选基因策略迄今已鉴定了数十种原发性高血压的相关基因。本文对其中研究最为深入的 8种基因在近期的研究进展作一综述。     

WNK4基因单核苷酸多态性与原发性高血压相关性研究进展

<正>原发性高血压(Essential hypertension,EH)是遗传因素和环境因素共同作用的结果,家族和流行病学研究显示30%～50%的EH患者受遗传因素的影响[1-2]。目前对EH的分子致病机制还所知甚少。高血压相关基因单核苷酸多态性(single nucleotide polymorphism,SNPs)的筛查及关联分析,是研究     

髓过氧化物酶基因多态性与原发性高血压遗传易感性的研究

目的:研究髓过氧化物酶(MPO)基因多态性与原发性高血压(EH)之间的遗传易感性.方法:采用分子流行病学方法,应用聚和酶链反应检测法107例EH和97例健康对照MPO基因型,比较不同基因型之间的分布频率及95%可信区间(CI),分析MPO基因多态性与EH易感性的关系.结果:正常人群GG、GA、AA基因型频率分别为56 7%、40 2%和3 1%,EH组分别为70 1%、29 0%和0 9%.携带GG者患EH的风险是基因型为至少一个等位基因A者的1 79倍 (95%CI 1 005~3 186).结论:本研究人群MPO基因多态与EH遗传易感性相关,等位基因A对EH易感性有保护作用.     

Lipid profile and apolipoprotein E polymorphism in essential hypertension

BACKGROUND: Studies in several populations have indicated that genetic variation at the apolipoprotein E structural locus influences atherosclerosis leading to cardiovascular diseases. The possible role of apolipoprotein E polymorphism in the development of essential hypertension has not been sufficiently investigated. In this case-control study, we aimed to determine the significance of association between essential hypertension and apolipoprotein E genotypes. In addition, apolipoprotein E genotypes were correlated with serum lipid levels in order to understand the possible interaction between the specific genotype and the lipid profiles that can contribute to hypertension. METHODS AND RESULTS: The apolipoprotein E genotypes were assayed in 185 patients and 200 controls by polymerase chain reaction followed by enzymatic digestion with Hha I. Using logistic regression analysis, the multivariate-adjusted odds of hypertension were calculated. The incidence of epsilon4 allele was found to be significantly higher in patients (12.16%) than in controls (5.75%, chi2=10.87; p<0.05) and also in patients with positive family history (16.7%) as compared to negative family history (8.87%, chi2 = 8.45; p<0.1). Further, it was observed that carriers of epsilon4 allele have twice as much risk (p<0.05) for developing hypertension as compared to carriers of other alleles. Patients with epsilon4 allele had significantly higher levels of total cholesterol and low-density lipoprotein- cholesterol as compared to epsilon4 allele non-carriers (p<0.05). The adjusted odds ratios for epsilon4 and epsilon2 alleles versus epsilon3 allele were 2.2 (95% confidence interval 1.2 to 3.8, p<0.05) and 1.2 (95% CI, 0.75 to 1.77, p<0.514), respectively. CONCLUSIONS: Our study revealed a strong association of apolipoprotein E locus with hypertension and lipid profile. However, large population-based studies are needed to understand the exact role played by the locus in causing the condition.     

基质金属蛋白酶-9基因多态性与原发性高血压发病的相关性

目的基质金属蛋白酶（MMP）-9是一种基质降解酶,可能参与了血管的重构。本研究旨在探讨MMP-9基因C-1562T多态性与高血压及性别的相关性。方法采用聚合酶链反应结合限制性内切酶片段长度多态性分析,分别检测北京宣武医院门诊807例原发性高血压患者和同一地区509例正常对照的MMP-9基因C-1562T多态性。电泳判断基因型并测序。结果高血压组TT＋CT基因型频率和T等位基因频率显著高于正常对照组（28．7％vs22．6％,15．4%vs12．7％;P〈0．05）。女性中高血压组的TT＋CT基因型频率和T等位基因频率显著高于正常对照组（31．0％vs22．0％,16．6％vs12．1％;P〈0．05）,T等位基因对高血压的OR值为1．442（CI：1．057～1．968）。男性中两组基因型无显著差别。老年女性高血压组的TT＋CT基因型频率和T等位基因频率显著高于老年男性高血压组、老年女性正常对照组和非老年女性高血压组。结论MMP9基因-1562T等位基因可能是老年女性原发性高血压的危险因素。     

肾素-血管紧张素系统基因多态性与原发性高血压的关系

原发性高血压是一种多基因病,受遗传以及外界多种因素的影响,本文介绍了影响原发性高血压基因中的肾素-血管紧张素系统基因,分别就肾素基因、血管紧张素原基因、血管紧张素转换酶基因、血管紧张素受体基因的研究进展作一综述.     

神经前体细胞表达发育调控样蛋白4基因多态性与哈萨克族高血压病的关联研究

目的 研究神经前体细胞表达发育调控样蛋白4基因(NEDD4L)变异与哈萨克族高血压病的相关性.方法 采取以人群为基础的横断面病例-对照研究方法 .采用TaqMan PCR技术对rs4149601多态性在哈萨克族自然人群中(883例;男性375例,女性508例;高血压383例,对照500例)进行分型;分析该多态性与哈萨克族高血压病的相关性;然后联合分析rs4149601与既往采用直接测序法在本人群中发现的NEDD4L基因3个代表性变异位点(296921-296923delTTG,rs2288774和rs2288775)组成的单体型与哈萨克族高血压病的相关性.结果 (1)rs4149601多态性的基因型、等位基因的分布符合Hardy-Weinberg平衡,3个代表性多态位点与rs4149601多态性间未发现有意义的连锁不平衡(r2＜0.8＝;(2)rs4149601多态性的基因型、等位基因在高血压组、对照组分布差异无统计学意义;(3)在总体、男性中,rs4149601,296921-3delTTG,rs2288774和rs2288775四个多态位点组成的单体型在高血压组、血压正常组分布差异无统计学意义;在女性中,D-C-G-G(296921-3delTTG/rs2288774/rs2288775/rs4149601)单体型在高血压组的频率高于血压正常组,且差异有统计学意义(P=0.026).结论 rs4149601多态性与哈萨克族高血压病不相关;D-C-G-G(296921-3delTTG/rs2288774/rs2288775/rs4149601)单体型可能是新疆哈萨克族人高血压病的易感因素.     

Alpha-adducin Gly460Trp polymorphism and renal hemodynamics in essential hypertension

Previous studies have shown an association between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. Not much is known about the effects of the variants of this polymorphism on renal hemodynamics and function. Therefore, we performed the present study to investigate the effect of the 460Trp allele of the alpha-adducin gene on renal hemodynamics in one hundred and seventeen essential hypertensive patients who were put on a low and high sodium diet (randomized order). On the last day of each one-week dietary period, blood pressure, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and neurohormones were measured. Effective renal blood flow (ERBF), renal vascular resistance, and filtration fraction were calculated. ERPF, ERBF, and GFR were lower in patients homozygous for the 460Trp allele compared with patients with the Gly460Gly genotype on low sodium diet but no differences were found at the higher sodium intake. On the other hand, levels of atrial natriuretic peptide were significantly higher in patients with the Trp460Trp genotype as compared with patients with the Gly460Gly genotype on both diets. In multivariate analysis, Trp460Trp genotype, age, and mean arterial pressure were predictors of ERPF, whereas Trp460Trp genotype and age were predictors of GFR during the phase of low sodium diet. The present study shows that the Trp460Trp genotype is significantly associated with reduced renal plasma flow and glomerular filtration rate as compared with the wild-type variant.     

eNOS基因多态性与湖北汉族人群原发性高血压相关

采用聚合酶链反应结合聚丙烯酰胺凝胶电泳检测湖北汉族316例原发性高血压患者和338名正常人内皮型一氧化氮合酶(eNOS)基因第4内含子多态性,发现eNOS基因该位点多态性(ab+aa等位基因)与原发性高血压显著相关(P＜0.05),可能是湖北汉族人群原发性高血压的一个易感标记.     

Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15–1.45), CT 1.14(1.00–1.28), and TT 0.94(0.68–1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.     

Dopamine D1 receptor gene polymorphism is associated with essential hypertension

Dopamine has been shown to influence renal sodium excretion through a direct interaction with the dopamine receptor (DR). The dopamine D1 receptor (DRD1) has been localized to the proximal tubules and is known to increase sodium excretion by inhibiting Na-H exchanger and Na,K-ATPase activity. Defective renal dopamine production and/or DR function have been reported in essential hypertension (EH) as well as in genetic models of animal hypertension. With a restriction fragment length polymorphism of the DRD1 gene, we performed an association study in patients with EH. One hundred thirty-one subjects with EH and 136 age-matched normotensive (NT) controls were studied. Polymerase chain reaction was used to amplify the A-48G polymorphic site in the DRD1 gene, and restriction analysis of the polymerase chain reaction product was used to score the A and G alleles. The allele frequencies in the EH group and NT group were then compared. The G allele was observed more frequently in the EH group than in the NT group, and the allele frequencies in the 2 groups differed significantly (chi(2)=6.5, P=0.01). Multiple logistic linear regression analysis revealed that the genotype frequencies of A/A, A/G, and G/G differed significantly (odds ratio=2.1; 95% CI=1.19 to 3.66) between the EH and NT groups. EH patients who possess the G allele had a higher diastolic blood pressure than those lacking the G allele (P<0.01). Thus, the alleles detected by this restriction fragment length polymorphism in the DRD1 gene are associated with EH, and they appear to influence the diastolic blood pressure of Japanese EH patients.     

内皮型一氧化氮合酶基因rs3918181位点多态性与原发性高血压的关系研究

目的 探讨天津市汉族人群内皮型一氧化氮合酶(eNOS)基因第14内含子rs3918181位点多态性与原发性高血压(EH)的关系.方法 采用聚合酶链反应-限制性内切酶片段长度多态分析法(PCR-RFLP)对290例EH患者和161名健康对照者的eNOS基因rs3918181位点进行基因多态性分型,同时检测所有研究对象的血脂等危险因素,分析不同基因型与EH发病的关系.结果 两组年龄、体质指数的差异有统计学意义(均为P＜0.05).EH组患者的AA、AG和GG基因型分布频率分别为0.293、0.393和0.314,对照组分别为0.180、0.472和0.348,两组相比差异有统计学意义(均为P ＜0.05);EH组A与G等位基因频率分别为0.490和0.510,对照组分别为0.416和0.584,两组相比差异有统计学意义(均为P ＜0.05).影响EH的危险因素有年龄、体质指数.结论 eNOS基因rs3918181位点多态性与EH相关.