汉族人群血管紧张素转换酶基因插入/缺失(I/D)的遗传多态性

背景:血管紧张素转换酶是肾素-血管紧张素-醛固酮系统的重要组成部分,血管紧张素转换酶基因第16内含子内存在一个287bp的Alu序列的插入/缺失(I/D)多态性,与心血管疾病、IgA肾病等疾病的发生具有一定的相关性。目的:分析汉族人群血管紧张素转换酶基因插入/缺失(I/D)多态性的分布,并与已知的其他种族人群进行比较。设计:以健康汉族人为观察对象的观察性实验。单位:江苏省临床免疫学重点实验室,苏州大学附属第一医院检验科,江苏大学医学技术学院检验系。对象:受检者为2005-12/2006-01苏州大学附属第一医院门诊健康体检者241名,男152名,女89名,平均年龄(27±8)岁,均为无血缘关系的苏州地区汉族人,经临床及实验室检查确认排除肝、肾、内分泌、心脑血管疾病。方法:应用聚合酶链反应检测了241名汉族健康体检者血管紧张素转换酶基因I/D多态性等位基因的基因型,并采用荧光标记末端终止法对基因型为D/D、I/I的PCR纯化产物进行DNA测序确认。主要观察指标:血管紧张素转换酶基因I/D基因型,等位基因频率以及与其他种族人群的比较。结果:241名受检者全部进入结果分析。①血管紧张素转换酶的基因型表现为缺失纯合子(DD)、插入纯合子(II)以及缺失和插入杂合子(DI),等位基因D较等位基因Ⅰ缺失一段287bp的核苷酸,即Alu序列。②II,ID,DD基因型频率分别为46.1%,41.5%,12.4%;等位基因I,D频率分别为66.8%,33.2%。③日本人与汉族人群血管紧张素转换酶基因型分布相似,均以II型最常见,DD型最少;欧美人群以ID居多,II型较少。汉族人群与日本人及欧美人群血管紧张素转换酶基因型频率的分布具有种族差异性。与其他各民族人群比较,汉族人群等位基因I显著高于上述各民族(χ2=105.55,P<0.01),等位基因D明显较低(χ2=87.54,P<0.01)。结论:血管紧张素转换酶基因多态性具有种族差异性。了解不同种族人群间血管紧张素转换酶基因多态性的遗传特点,是研究血管紧张素转换酶基因I/D多态性与疾病相关性的基础和前提。

Genetic polymorphism of angiotensin-converting enzyme gene insertion/deletion in Chinese Han population

BACKGROUND: The angiotensin-converting enzyme (ACE) is the important component of the renin-angiotensin-aldosterone system (RAS). The ACE gene has, in fact,insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence. ACE gene heterozygotes insertion/deletion (I/D) polymorphism is correlated with cardiovascular disease and IgA nephropathy and other diseases. OBJECTIVE: To investigate the distribution of ACE gene I/D polymor-phism in Chinese Han population in comparison with other known ethnic populations. DESIGN: Observation study on healthy individuals of Han nationality. SETTING: Key Laboratory of Clinical Immunology of Jiangsu Province; Department of Laboratory Medicine, First Hospital Affiliated to Soochow University; Department of aboratory Medicine, College of Medical Technology of Jiangsu University PARTICIPANTS: Totally 241 healthy individuals who received the healthy examination in the First Hospital of Soochow University between December 2005 and January 2006 were recruited in the experiment. They were 152 male and 89 female , with mean age of (27±8)years. All the participants without blood relationship were Han nationality from Suzhou region in China, free from disorder of hepatic, renal, endocrine and cardio- cerebrovascular diseases which were confirmed by clinical and experimen- tal examination. METHODS: Genotype of ACE gene I/D polymorphism allele of 241 healthy individuals of Han nationality was detected with polymerase chain reaction (PCR). PCR purified products with genotype of deletion/deletion (DD) and insertion/insertion (Ⅱ) polymorphism were performed DNA sequencing with fluorescence-labeled end termination method. MAIN OUTCOME MEASURES: Genotype and allele frequency of ACE gene I/D, as well as the comparison between them and those of other ethnic population. RESULTS: All the 241 subjects participated in final result analysis. ① The genotypes of ACE were DD, Ⅱ and ID. Compared with allele Ⅰ, allele D lost 287-base pair Alu repeat sequence. ②The frequencies of genotype Ⅱ, ID and DD were 46.1％, 41.5％ and 12.4％ respectively, with an allelic frequency of 66.8％ for allele Ⅰ and 33.2％ for allele D. ③The distribution of ACE genotype was similar between Japanese and Han nationality crowd, both presenting that type Ⅱ was commonly seen and type DD was the least; ID was mostly found in European and American crowd, but Ⅱ was little found. There was racial diversify of frequency of the distribution of ACE genotype among individuals of Han nationality and Japanese as well as Europeans and Americans. Compared with other nationalities, allele Ⅰ of individuals of Han nationality was significantly higher than that of above nationalities (χ2=105.55,P ＜ 0.01), but allele D was obviously lower (χ2=87.54,P ＜ 0.01). CONCLUSION: ACE gene polymorphism has racial diversify. To know genetic features of ACE gene polymorphism of individuals of different na tionalities is the basis and prerequisite to study the correlation of ACE gene I/D polymorphism with diseases.