AGT基因rs1926723、rs699及rs4762多态性与肺血栓栓塞症的相关性研究

摘要

目的 探讨中国汉族人血管紧张素原(AGT)基因3个常见变异位点rs1926723、rs699和rs4762与肺血栓栓塞症(PTE)易感性的关系.方法 将确诊的95例PTE患者作为PTE病例组,均来自无血缘关系的汉族人群;163例健康人作为对照组.采集上述人员空腹静脉血0.5 mL,用BioChain全血基因组DNA提取试剂盒提取基因组DNA,紫外分光光度计定量.挑选AGT基因中次要等位基因频率(MAF)>0.05的3个常见单核苷酸多态性位点(rs1926723、rs699和rs4762),经聚合酶链反应(PCR)-Sanger法测序验证,比较两组人员各位点基因型及等位基因分布频率的差异,通过Haploview 4.2软件分析其连锁不平衡性及单倍型与PTE的相关性.结果 AGT基因rs1926723(C/T)及rs699(A/G)位点在PTE病例组和对照组间的分布均存在显著性差异(P<0.05);rs1926723中TT基因型及rs699中GG基因型与PTE的发生呈负关联,OR(95%CI)分别为0.484(0.289～0.810)和0.463(0.263～0.816);调整年龄、性别混杂前后,rs4762(G/A)位点在PTE病例组和对照组间的分布均无显著性差异(P>0.05).PTE病例组和对照组中T-G-G单倍型的分布存在显著性差异[P<0.05,OR(95%CI):0.493(0.342～0.710)].结论 AGT基因rs1926723及rs699位点的变异与PTE相关,rs1926723中TT基因型携带、rs699中GG基因型携带及单倍型T-G-G携带可预示较低的PTE发病风险.%Objective To elucidate the relationship of three common variation loci of angiotensinogen (AGT ) gene (rsl926723 , rs699 and rs4762) in Chinese Han people with pulmonary thromboembolic disease (PTE) susceptibility .Methods Ninety-five patients with confirmed PTE which had been selected from Chinese Han population without blood relationship served as PTE group , while 163 healthy people as control group .0 .5 mL of fasting venous blood was collected from above-mentioned people .Genomic DNA was extracted using BioChain whole blood genomic DNA extraction kit and quantified by ultraviolet spectrophotometer .Three common loci(rsl926723 ,rs699 and rs4762) with single nucleotide polymorphism and minor allele frequency over 0 .05 in AGTgene were selected and sequenced by polymerase chain reaction (PCR)-Sanger method .Differences of genotypes of each locus and allele frequencies of people in the two groups were compared ,and the correlation of their linkage disequilibrium and haplotype with PTE were analyzed by Haploview 4 .2 software .Results Distributions of rsl926723(C/T) and rs699(A/G) in AGT gene of people between PTE group and control group showed significant difference (P<0 .05) ,rsl926723 with genotype TT and rs699 with genotype GG were negatively related to PTE occurrence[OR(95% CI)were 0 .484(0 .289—0 .810) and 0 .463(0 .263—0 .816),respectively]. Distributions of rs4762(G/A) between PTE group and control group demonstrated no significant difference (P<0 .05),while that of T-G-G hyplotype between PTE group and control group exited significant difference [P<0 .05 ,OR(95% CI) ,0 .493 (0 .342 — 0 .710)] .Conclusion rsl926723 and rs699 loci variation in A GT gene are associated with PTE ,rsl926723 with genotype TT ,rs699 with genotype GG and T-G-G hyplotype can indicate the low risk of PTE onset .