血管紧张素原基因核心启动子区域的单核苷酸多态与冠心病的关系

Association of single nucleotide polymorphisms in the 5'upstream core promoter region of angiotensinogen gene with coronary heart disease

目的:在中国南方汉族人群中,检测血管紧张素原基因(AGT)5'端核心启动子内AGCE1区域的单 核苷酸多态(SNPs),并探讨其与冠心病发病的关系。方法:应用PCR直接测序技术检测AGCE1区域的序列,并 结合多重SNaPshot反应在145例血压正常的冠心病患者和185例健康对照者中对所检测的SNPs进行基因分 型。结果:在AGT基因AGCE1区域-20和-6位上发现2个SNPs,且A 20C和G 6A多态呈连锁不平衡。A 20C多态的基因型分布在冠心病组(CC=4,AC=29,AA=112)和对照组(2,61,122)之间差异有统计学意义(P <0.05)。C等位基因频率在两组间虽有差异(12.76%/17.57%),但未达到统计学意义(P>0.05)。G 6A多态 的基因型分布和等位基因频率在冠心病组与对照组之间差异均无统计学意义。单倍型分析表明,各组单倍型的 频率分布在两组间差异亦无统计学意义。结论:AGT基因的A 20C多态可能与血压正常人群的冠心病发病相 关。

Objective:To detect single nucleotide polymorphisms(SNPs) in angiotensinogen(AGT) core promoter element 1 (AGCE1) located in the 5'upstream core promoter region(position -25 to -1) of AGT gene and evaluate their associations with the occurrence of coronary heart disease(CHD) in south chinese han population. Method:SNPs detection in AGCE1 of AGT gene was performed by PCR-sequencing. The genotype was analysed by the method of SNaPshot Multiplex Kit in 145 normotensive patients with CHD and 185 healthy controls. Result:Two SNPs at position -6 and -20 were detected in AGCE1 which exhibited significant linkage disequilibrium.The genotype distribution of A-20C polymorphism were obviously different between group of CHD (CC=4,AC=29,AA=112) and group of controls (2,61,122,P< 0.05). Frequency of C allele was different between two groups ( 12.76% vs 17.57%),but no statistical difference was found (P> 0.05). However,the genotype distribution and allele frequency of G-6A polymorphism had no significant difference between two groups.In the haplotype analysis, the haplotype frequencies of A-20C and G-6A polymorphism were similar between two groups. Conclution: A-20C polymorphism of AGT gene might be associated with the occurrence of CHD in normotensive population.