血管紧张素转化酶1基因单倍型与原发性高血压

Association between haplotypes of ACE1 gene and essential hypertension

目的:研究中国人群中血管紧张素转化酶1(ACE1)基因多态性及单倍型与原发性高血压的关系。方法:在298例原发性高血压患者(病例组)与199例血压正常人(对照组)采用PCR后的限制性酶切片段长度多态性(PCR-RFLP)法或电泳直接检测ACE1基因8个位点多态性,同时用最大期望值(EM)计算法进行2位点连锁不平衡(LD)状态和单倍型类型的估计。结果:ACE1基因多态存在LD(均D'>0.5),8个多态存在于常见的9个单倍体中,其中2种最常见的单倍型为A(A-T-A-T-G-I-A-3)和B(C-C-T-C-A-D-G-2),A和B在每个位点都不相同。单个位点除A-240T外,其余各位点均未见与高血压有关联,单倍型D的频率在病例组中高于对照组。结论:该群体中ACE1基因存在LD,T-240位点可能为原发性高血压易感位点LD。

Objective： To investigate the relationship between polymorphisms of the angiotensin-1 converting enzyme （ACE） gene and the risk for hypertension in a Chinese population, Method：A-5499C, T-3897C, A-240T. T1237C. G2215A, I/D of Alu fragment in intron 16, G2350A. 4656（CT）3/2 were detected by PCR combined with restriction enzyme digestion or electrophoresis. By using maximum likelihood estimation （MLE）, the pattern of intragenic linkage disequilibrium and the haplotype structure were estimated. Result： All the eight polymorphism pairs exhibited significantly lingkage disequilibrium. Nine common haplotypes from 8 sites of the ACE1 gene were observed. The two most frequenthaplotypeswereA（A-T-A-T-G-I-A-3） andB（C-C-T-C-A-D-G-2）. HaplotypeA and haplotype B were different with each other at all eight sites. All the loci constituting the haplotype A were individually associated with low ACE1 activity haplotypes. Except for A-240T and haplotype D, no other singlelo cus or haplotype frequencies were different significantly between the patient and control groups. Conclusion： Nine major haplotypes constructed by 8 polymorphism loci account for most of the variation in ACE1. T-240 site of ACE1 may increase the risk of EH.