高血压相关基因HSG上游调控序列单核苷酸多态性的发现及其与高血压的关联

首都医科大学学报 ›› 2004, Vol. 25 ›› Issue (4): 464-468.

高血压相关基因HSG上游调控序列单核苷酸多态性的发现及其与高血压的关联

王佐广¹, 温绍君¹, 陈光慧², 张维君¹, 文杰¹, 吴兆苏¹, 罗毅¹, 汤健²

1. 北京市心肺血管疾病研究所首都医科大学附属北京安贞医院高血压研究室;2. 北京大学医学部心血管基础研究所

收稿日期:2004-02-18 修回日期:1900-01-01 出版日期:2004-10-15 发布日期:2004-10-15

Discovery of Single Nucleotide Polymorphism in HSG Gene in Hypertensive Patients and its Relationship with Hypertension

Wang Zuoguang¹, Wen Shaojun¹, Cheng Guanghui², Zhang Weijun¹, Wen Jie¹, Wu Zhaosu¹, Luo Yi¹, Tang Jian²

1. Division of Hypertension, Beijing Institute of Heart, Lung, Vascular Disease, Affiliate of Capital University of Medical Sciences;2. Basal institute of vascular diseases, Department of Medicine, Beijing University

Received:2004-02-18 Revised:1900-01-01 Online:2004-10-15 Published:2004-10-15

摘要/Abstract

摘要： 通过研究不同人群中新发现的高血压相关基因HSG基因多态性,以揭示高血压相关基因多态性与高血压的关系.选取74例正常对照,其中男性38例,女性36例,平均年龄(54.15±7.77)岁;原发性高血压患者51人,其中男性27人,女性24人,平均年龄(57.25±7.97)岁;高血压家族患者20例,其中女性11人,男性9人,平均(49.97±6.93)岁.取外周静脉血并提取DNA,进行PCR扩增法获得相应的产物,应用DNA测序法直接得到PCR产物的核苷酸序列后比较不同人群的该片段的碱基组成及其特征.结果:肌酐(Cr)和尿素氮(BUN)在高血压组明显高于正常血压组,而高血压组和高血压家族组的收缩压和舒张压均明显高于正常血压组(P<0.01,P<0.05);高血压组的血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET)、利钠多肽(心钠素,ANP)及降钙素基因相关肽(CGRP)质量浓度均高于正常血压组,且两者之间存在着明显的差异(P<0.01);HSG基因12位内含子的140位点在3种人群中存在G点删除变异.且其基因频率在高血压家族组、高血压组、正常人之间存在着明显的差别(0.80、0.41、0,P<0.001).提示:肾功能的指标(Cr和BUN)可能可以较早地反映高血压的进展和靶器官损害状况.血浆AngⅡ、ET、ANP及CGRP质量浓度在不同血压的人群中存在着明显的差别.逐步回归分析表明收缩压与年龄明显正相关(R＝0.387,P<0.001);舒张压与AngⅡ、Cr、BUN明显正相关(R＝0.328、0.289、0.165,P<0.001),而与高密度脂蛋白胆固醇(HDLC)呈负相关(R＝-0.149,P<0.01).HSG基因12位内含子的140位点的基因频率在不同的人群中存在着明显的差别,该基因的多态性可能是高血压独立危险因素.

关键词: 高血压, HSG基因, 血管活性因子, 单核苷酸多态性

Abstract: The aim was to investigate the single nucleotide polymorphism(SNP) of the novel hyperplasia suppressor gene (HSG) and uncover the relationship of HSG SNP and hypertension. Altogether 74 normaltensive people (male 38, female 36), 51 essential hypertensive patients(male 27, female 24),which came from the outward patients of Anzhen hospital, and 20 patients of hypertension with family history (male 9, female 11) were chosen. Respectively, the average age was 54.15±7.77, 57.25±7.97 and 49.97±6.93. Patients vein blood was drawn and DNA was extracted, then the right primers and PCR were designed. The sequences of each PCR-product were sequenced by ABI PRISM 377-DNA sequencer. Cr and BUN were high in hypertensive patients than in normaltensive patients (P<0.01).The level of AngⅡ, ET were higher significantly in normaltensive(P<0.01, P<0.01) while ANP and CGRP were lower in hypertensive patients than in moraltensive patients(P<0.05, P<0.01), though no obvious differences existed in hypertensive patients with family history and the normal control group. Systolic pressure was closely related to age (R=0.387;P<0.001). Diastolic pressure was positively related to AngⅡ,Cr,BUN(R=0.328,0.289,0.165;P<0.001),though was negatively related to HDLC(R= -0.149,P<0.01) There was obvious difference in the 140 nucleotide of the 12th intron nucleotide of HSG in normaltensive, hypertensive patients and patients with family history (0.80,0.41,0;P< 0.001). Probably, Cr and BUN were a sign of hypertension and its complication. Some vasoactive factors may be important in the origin and development of primary hypertension. There was a G-deletion SNP of 12th intron nucleotide of HSG in Chinese, and perhaps the SNP was an independent risk factor for hypertension.

Key words: hypertension, HSG, vasoactive factor, single nucleotide polymorphism

中图分类号:

R544.1

王佐广;温绍君;陈光慧;张维君;文杰;吴兆苏;罗毅;汤健. 高血压相关基因HSG上游调控序列单核苷酸多态性的发现及其与高血压的关联[J]. 首都医科大学学报, 2004, 25(4): 464-468.

Wang Zuoguang;Wen Shaojun;Cheng Guanghui;Zhang Weijun;Wen Jie;Wu Zhaosu;Luo Yi;Tang Jian. Discovery of Single Nucleotide Polymorphism in HSG Gene in Hypertensive Patients and its Relationship with Hypertension[J]. Journal of Capital Medical University, 2004, 25(4): 464-468.

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