【作者】 杨红菊； 郑尚永； 肖春杰；

【Author】 YANG Hong-Ju,ZHENG Shang-Yong,XIAO Chun-Jie School of Medicine,Yunnan University,Kunming,Yunnan 650091,China

【机构】 云南大学医学院；

【摘要】 血管紧张素Ⅱ是RAAS系统的生物活性中心,主要与AGTR1受体结合发挥血管收缩、水钠潴留、促进醛固酮分泌等生物学效应。因此,AGTR1基因是原发性高血压的重要候选基因。本文应用PCR-RFLP研究方法,对云南哈尼族346例原发性高血压患者和346例对照,彝族303例原发性高血压患者利312例对照样本进行了AGTR1基因12个SNPs的多态性检测。单位点分析显示,哈尼族人群AGTR1基因rs2638360 C等位基因和rs275653 C等位基因增加哈尼族女性人群原发性高血压的患病风险。彝族人群rs387967 C等位基因使彝族混合群体高血压患病相对风险度显著降低。rs385338 G、rs5186 c和rs2638360 C等位基因使彝族男性患高血压的相对风险度显著升高而rs387967 C等位基因使彝族女性患高血压的相对风险度显著降低。通过单位点基因型组间血压水平的差异分析发现,在未接受降压治疗的哈尼族和彝族人群中,血压升高与携带风险性等位基因基因型相关。单倍型分析结果表明,哈尼族人群单倍型HY10携带者患高血压的风险增高,彝族人群单倍型HH9携带者患高血压的风险增高。多位点间相互作用MDR分析显示,哈尼族群体AGTR1基因多位点间交互作用未发现与原发性高血压的发生相关;彝族群体rs387967和rs12695908是多位点相互作用的最佳模型,存在交互作用影响高血压发生。结果提示,AGTR1基因与两个民族原发性高血压发生相天,并且呈现出不同民族、不同性别具有不同高血压诱导或保护多态化位点的特点。更多还原

【Abstract】 Essential hypertension is a complex disease,caused by inheritance of several susceptible genes and multiple environmental determinants.Renin-angiotensin-aldosterone system(RAAS) plays an important role in blood pressure regulation and those genes encoding RAAS components are considered as attractive candidate genes for essential hypertension.AGTR1 receptor mediates most of the known effects of angiotensinⅡ,such as vasoconstriction,stimulation of Na~+ reabsorption,and aldosterone secretion.In the present study,12 SNPs were genotyped in Hani (case=346,control=346) and Yi(case=303,control=312) populations by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),using the case-control strategy. The results are as follows:As to the AGTR1 gene,single site analyses indicated that rs2638360 C allele significantly increased the risk of EH with no gender disparity in Hani population.In Hani population,the rs275653 C allele significantly increased the risk of EH in females.In Yi population, the rs387967 C allele significantly reduced the risk of EH.The rs385338 G、rs5186 C and rs2638360 C alleles significantly increased the risk of EH in Yi males.The rs387967 C alleles were significantly related to EH in females.These results indicated that each population has its own group of disease-associated SNPs.In all Hani and Yi subjects,who did not received the anti-hypertension therapy,the BP presented a rising trend associated with the genotypes in the following order:the homozygous genotype without the susceptible allele,the heterozygous genotype,the homozygous genotype with the susceptible allele.This finding indicated that the elevated BP was associated with genotypes with the susceptible allele.Similarly,the BP with a declining trend was correlated to genotypes with the protective allele.The haplotype analyses indicated that the AGTR1 HY4 and HY5 haplotype significantly decreased the risk of EH,and the HY10 haplotype increased the risk of EH in Hani population.In Yi population,the AGTR1 HH5,and HH10 haplotypes were found to decrease the risk of EH significantly,the HH9 haplotype was found to significantly increase the risk of EH.SNP-SNP interactions were not detected AGTR1 and EH by multifactor- dimensionality reduction(MDR) method in Hani.Further multifactor-dimensionality reduction(MDR) analysis revealed a significant two-loci(rs387967和rs12695908) combination to be an optimal model and demonstrated the SNP-SNP interactions between the AGTR1 gene polymorphisms and essential hypertension.更多还原