新疆哈萨克族原发性高血压易感基因的关联分析

Study on the association of predisposing genes with essential hypertension among Kazakhs ethnic group in Xinjiang

目的探讨血管紧张素原（AGT）基因第二外显子M235T和上游启动子区G-6A、血管紧张素转换酶（AcE）基因插入／缺失、内收蛋白α亚单位（ADD1）基因第10外显子Gly460Trp、G蛋白β3亚单位（GNB3）基因第10外显子C825T此5个位点的多态性与新疆哈萨克族原发性高血压病之间的关系以及基因与基因、基因与环境间的交互作用。方法应用病例对照研究设计，原发性高血压组241例，对照组200例。所有研究对象均进行常规体检及体质测量，并采集空腹静脉血进行血糖、血清胆固醇、TG等检测。应用PCR—RFLP对病例组和对照组的上述位点多态性进行检测。结果各多态型的分布均符合Hardy—Weinberg平衡。两组等位基因频率和基因型分布比较，M235T等位基因频率差异有统计学意义（P=0．0483），其他位点等位基因频率和基因型分布差异无统计学意义。多元logistic回归分析各多态位点均有统计学意义。MDR分析4因子（AGE／CHO／G-6A／ACE）为最佳模型。结论所研究的4个基因均可能是与哈萨克族原发性高血压发病相关的基因，AGT、ACE、年龄、胆固醇可能存在一定的交互作用。

Objective To investigate the association between M235T and G-6A polymorphism of AGT gene, insertion/deletion （I/D） polymorphism of ACE gene, Gly460Trp polymorphism of ADD1 gene, C825T polymorphism of GNB3 gene and essential hypertension in Xinjiang Kazakhs group as well as to identify the interactions of gene-gene and gene-environment. Methods A case-control study （ n = 441 ） was performed in 241 cases and 202 controls. Polymerase chain reaction and restrict fragment length polymorphism （PCR-PFLP ） technique were used to detect the genotypes polymorphism. Results Comparing the frequencies of alleles and genotypes, there were no statistical significances except frequency of allele of M235T （ P = 0. 0483） identified. In logistic regression analysis, there were significant differences in all of the loci. The 4 loci model （AGE/CHO/G-6A/ACE） appeared the best model in MDR analysis. Conclusion Our research data showed that the polymorphisms of all the four genes might be associated with hypertension in the Kazakhs group of Xinjiang while there might be interactions existed in AGT, ACE, AGE and CHO.