偶合基本氨基酸裂解酶4基因多态性与高血压的相关性研究  

The association of a polymorphism in the paired basic amino acid cleaving enzyme 4 gene and hypertension

作　　者：李建平[1] 王晓滨[2] 陈常忠[3] 徐新[3] 冯雁[3] 洪秀梅[4] 龙华[4] 徐希平[3] 霍勇[1] 

机构地区：[1]北京大学第一医院心内科,100034 [2]波士顿大学医学中心儿科 [3]哈佛大学公共卫生学院群体遗传研究室 [4]安徽大学生物医学研究所

出　　处：《中华心血管病杂志》2004年第9期781-785,共5页Chinese Journal of Cardiology

摘　　要：目的　研究高血压易感位点 2 (HYT2 )内人类偶合基本氨基酸裂解酶 4 (PACE4 )基因多态性与高血压的关系。方法　在两个相互独立的人群中 ,分别采用病例 对照的研究方法 ,研究PACE4基因内 7个单核苷酸多态性 (SNP)与高血压的相关性。第一个研究人群包括 1 6 3例病例及1 2 5名对照 ,第二个人群包括 5 0 8例病例及 5 6 8名对照。我们在第一个人群中对PACE4基因 7个SNP与高血压的关系进行初步检测 ,并在第二个人群中进行验证。结果　在两个研究人群中均发现 ,PACE4基因rs1 871 977A/C多态性与高血压具有相关性。多因素Logistic回归显示 ,与CC基因型相比 ,AA基因型可以使高血压的危险性降低 :在第一个人群中 ,OR =0 2 ,95 %CI :0 1 - 0 6 ;在第二个研究人群中 ,OR =0 5 ,95 %CI :0 3- 1 0。多因素线性回归显示 ,携带AA基因型个体舒张压明显低于携带CC基因型个体 :在第一个人群中 ,β =- 1 4 9,SE =3 3;在第二个人群中 ,β =- 5 6 ,SE=2 3。结论　PACE4基因rs1 871 977A/C多态性可能通过与其附近的某一功能基因突变发生了连锁不平衡而成为高血压易感基因突变的标记物。本研究为今后在这一基因内寻找影响血压的基因突变提供了重要的线索。Objective To investigate the relationship between polymorphisms in the paired amino acid cleaving enzyme (PACE) 4 gene and hypertension. Methods In this casecontrol study two independent populations were used to analyze the association between 7 single nucleotide polymorphisms (SNP) and hypertension. There were 163 cases and 125 controls in population 1 and 508 cases and 568 controls in population 2, respectively. 7 SNPs were genotyped and their associations with hypertension were assessed in population 1, and evaluated again in population 2. Results SNP rs1871977 of PACE 4 gene was associated with hypertension in the two populations. Multivariate logistic regression analysis showed that compared to the CC genotype, the AA genotype was associated with a low risk of hypertension (in population 1, OR=0.2, 95% CI: 0.1-0.6; in population 2, OR=0.5, 95% CI:0.3-1.0). Multivariate linear regression analysis showed that compared to the CC genotype, the AA genotype was associated with a low diastolic blood pressure (in population 1, β=-14.9, SE=3.3; in population 2, β=-5.6, SE=2.3). Conclusions SNP rs1871977 of PACE 4 gene may be in linkage disequilibrium with a nearby functional mutation so that it seems to be a marker of hypertension susceptible gene mutation. The results of this study provided important clues for identifying mutation influencing blood pressure in this gene.

关 键 词：人群 高血压 基因多态性 对照 裂解酶 相关性研究 病例 单核苷酸多态性(SNP) 功能基因 氨基酸 

分 类 号：R544.1[医药卫生—心血管疾病] R512[医药卫生—内科学]