高分辨率熔解技术检测冠心病患者TNF-α及其受体基因多态性  

Genetic polymorphisms of TNF-α and its receptor genes detected by high resolution melting technology in the patients with coronary artery disease

作　　者：齐晓明[1] 张蕊[1] 李倩男[1] 卢明华[1] 尤崇革[1,2] 

机构地区：[1]兰州大学第二医院检验医学中心,兰州730030 [2]甘肃省消化系肿瘤重点实验室,兰州730030

出　　处：《临床检验杂志》2014年第6期405-409,共5页Chinese Journal of Clinical Laboratory Science

基　　金：教育部春晖计划项目(Z2010085);甘肃省技术研究与开发专项(1105TCYA002)

摘　　要：目的用高分辨率熔解(HRM)技术检测兰州地区汉族人群肿瘤坏死因子α(TNF-α)及其受体基因单核苷酸多态性(SNP),探讨其与冠心病(CHD)易感性及血脂指标的相关性。方法建立TNFA-238G>A、TNFA-308G>A、TNFA-857C>T、TNFA-863C>A、TNFR1-383A>C和TNFR2-exonT>G 6个SNP位点的PCR-HRM检测方法,并对207例CHD患者和274例健康对照进行病例-对照研究,分析其与CHD易感性及血脂指标的关系。结果仅TNFA-863C>A位点的基因频率和基因型频率在CHD组和对照组之间差异具有统计学意义(P=0.020,0.013),性别分层后仅存在于男性患者(P=0.026,0.018),CA基因型明显增加CHD患病风险(OR=1.999,P=0.029)。针对TNF-α基因的单倍型分析显示TNFA-238G/-308G/-857C/-863A(GGCA)单倍型明显增加CHD患病风险(OR=1.695,P=0.016)。病例组的血脂分析显示TNFR2-exon位点与CHD患者的高密度脂蛋白胆固醇(HDL-C)水平有关(F=5.126,P=0.024)。结论 TNFA-863C>A位点和单倍型TNFA-GGCA与兰州地区汉族人群CHD易感性相关,TNFR2-exonT>G位点与CHD患者HDL-C水平相关联。Objective To investigate the association of the single nucleotide polymorphism（SNP） of TNF-α and its receptor genes detected by high resolution melting（HRM） technology with the susceptibility of coronary heart disease（CHD） and serum cholesterol, triacylglycerol, HDL and LDL levels in HaM population of Lanzhou region. Methods The PCR-HRM assay was established and used to detect six SNPs of TNF-α and its receptor genes, including TNFA-238G 〉 A, TNFA-308G 〉 A, TNFA-857C 〉 T, TNFA-863C 〉 A, TNFR1-383A 〉 C and TNFR2-exonT 〉 G, in 207 CHD patients and 274 healthy controls. Then, the correlations of the six SNPs with the susceptibility of CHD and serum cholesterol, triacylglycerol, HDL and LDL levels were analyzed. Results Only the allele and genotype frequencies of TNFA-863C 〉 A were significantly different between CHD patients and the controls （ P = 0. 020 and 0. 013 ）. After stratified analysis by gender, it was found that the difference only existed in male patients（P = 0. 026 and 0. 018）. The CA genotype of TNFA-863 and the TNFA-238G/-308G/-857C/-863A（GGCA） haplotype were found to increase the risk of CHD development （OR = 1. 999, P = 0. 029; OR = 1. 695, P = 0. 016）. In addition, the SNP of TNFR2-exon was related to serum HDL level in CHD patients（ F = 5. 126, P = 0.024）. Conclusion The SNP of TNFA-863C 〉 A and the haplotype of TNFA-GGCA were associated with the susceptibility of CHD, and the SNP of TNFR2-exonT 〉 G was obviously related to serum HDL level of CHD patients in HaM population of Lanzhou region.

关 键 词：高分辨率熔解技术 肿瘤坏死因子Α 单核苷酸多态性 冠心病 

分 类 号：R541.4[医药卫生—心血管疾病]