端粒长度相关SNPrs621559和rs398652与中国人群冠心病易感性的关系  

Association of telomere length-related rs621559 and rs398652 genetic variants with susceptibility to coronary heart disease in the Chinese Han population

作　　者：王玉静[1] 谢晓莉[1] 陈书影[1] 叶季鲜[1] 郭文怡[2] 

机构地区：[1]中国人民解放军第三二三医院心血管内科,西安710054 [2]第四军医大学西京医院心血管内科,西安710032

出　　处：《岭南心血管病杂志》2016年第5期513-519,534,共8页South China Journal of Cardiovascular Diseases

摘　　要：目的 探讨端粒长度相关单核苷酸多态性（single nucleotide polymorphisms,SNP）与冠状动脉粥样硬化性心脏病（coronary heart disease,CHD）发病风险之间的关系。方法 采用病例对照研究,收集460例CHD患者和460例对照人群的外周血样本。荧光实时定量聚合酶链反应（polymerase chain reaction,PCR）检测平均端粒长度;运用Sequenom i PLEX分型技术对端粒长度相关的2个SNP位点进行基因分型;卡方检验分析SNP基因型在CHD组与对照组之间分布的差异;非条件Logistic回归分析SNP基因型与CHD发病风险的关系。结果 rs398652和rs621559基因型在CHD组和对照组中的分布具有显著性差异（P〈0.05）。rs398652和rs621559基因型与淋巴细胞端粒长度均显著相关,G等位基因型淋巴细胞相对端粒长度（relative telomere length,RTL）均较A等位基因型明显缩短（P〈0.05）。与携带AA基因型相比,携带rs398652和rs621559 G等位基因型人群的CHD发病风险显著增加,校正后OR值分别为1.98（95%CI：1.14-3.35）和1.57（95%CI：1.04-2.25）（P〈0.05）。分层分析发现,rs621559位点G等位基因型的CHD发病风险在原发性高血压（高血压）病史和糖尿病史亚群中显著增加（P〈0.05）,而rs398652位点G等位基因型的CHD发病风险在吸烟和血浆致动脉硬化指数〈-0.09亚群中显著增加（P〈0.05）。此外,rs398652位点基因型与吸烟之间存在显著的交互作用（Pinteraction=0.039）。结论 端粒长度相关SNP rs398652和rs621559与CHD的发生显著相关。Objectives To explore the correlation between telomere length-related single nucleotide polymorphisms （SNP） and susceptibility to coronary heart disease （CHD） in the Chinese Han population. Methods A systematic genetic analysis of telomere length-related SNPs was performed on 460 CHD cases and matched 460 controls. Genomic DNA was extracted from peripheral blood leukoeytes （PBLs） and genotyping was undertaken by Sequenom iPLEX system. The relative telomere length （RTL） was measured by quantitative real-time polymerase chain reaction in PBLs. The distribution differences of polymorphisms and related risk between CHD cases and controls were analyzed by the Chi-square test. The relationship of polymorphism genotype with the risk of CHD was analyzed by logistic regression. Results Genetic variants of rs398652 and rs621559 were significantly associated with leukocyte telomere length and susceptibility to CHD（all P〈0.05 ）. Individuals carrying G allele of rs398652 and rs621559 had a shorter leukocyte RTL compared to the A genotype （P〈0.05）. Compared with individuals carrying rs398652 and rs621559 AA genotype, individuals carrying G allele （AG＋GG） had a significantly increased risk of CHD （rs398652： adjusted OR=1.98, 95%CI= 1.14-3.35,P=0.006;rs621559： adjusted OR=l.57,95%CI=0.04-2.25,P=0.041）. Stratified analysis demonstrated that the association between rs621559 polymorphisms and CHD risk were more pronounced in hypertension and diabetes （all P〈0.05）, while the association between rs398652 polymorphisms and CHD risk were more pronounced in cigarette smoking and atherogenic index of plasma〈-0.09 （all P〈0.05 ）. Additionally, a statistical joint effect between the rs398652 genotypes and cigarette smoking might exist in elevating the risk of CHD （Pinteraction=0.039）. Conclusions The genetie variants of rs398652 and rs621559 may be associated with the risk of oceurrence of CHD in the Chinese Han population.

关 键 词：冠状动脉疾病 端粒长度 单核苷酸多态性 发病风险 

分 类 号：R541.4[医药卫生—心血管疾病]