GATA6基因启动区多态性与急性心肌梗死患者易感性和临床特征的相关性分析  

Correlation between GATA6 gene promoter region polymorphism and susceptibility and clinical features in patients with acute myocardial infarction

作　　者：孙兆庆 逄淑超 崔英华[3,4] 闫波 SUN Zhaoqing;PANG Shuchao;CUI Yinghua;YAN Bo(Cheeloo College of Medicine,Shandong University,Jinan,Shandong 250012,China;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment,Affiliated Hospital of Jining Medical University,Jining,Shandong 272029,China;Division of Cardiology,Affiliated Hospital of Jining Medical University,Jining,Shandong 272029,China;The Center for Molecular Genetics of Cardiovascular Diseases,Affiliated Hospital of Jining Medical University,Jining,Shandong 272029,China;Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine,Affiliated Hospital of Jining Medical University,Jining,Shandong 272029,China)

机构地区：[1]山东大学齐鲁医学院,山东省济南市250012 [2]济宁医学院附属医院山东省心脏疾病诊疗重点实验室,山东省济宁市272029 [3]济宁医学院附属医院心内科,山东省济宁市272029 [4]济宁医学院附属医院心血管疾病分子遗传学中心,山东省济宁市272029 [5]济宁医学院附属医院山东省中美转化医学合作研究中心,山东省济宁市272029

出　　处：《中国动脉硬化杂志》2019年第6期495-501,共7页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81370271;81400291;81670341;81870279)

摘　　要：目的探讨GATA6基因启动区-493(rs144923558)G/A、-172(rs146748749)G/A2个位点单核苷酸多态性(SNP)与急性心肌梗死(AMI)之间的关系及其相关的危险因素。方法采用病例-对照研究方法,收集328例AMI患者和344例正常对照;应用聚合酶链反应-限制性内切酶片段长度多态性技术结合DNA测序后的序列比对进行数据统计;运用Hardy-Weinberg平衡检验后,应用χ^2检验进行相关分析;利用Logistic回归对多种危险因素以及2个SNP位点与AMI发病进行关联性分析;利用Haplovview4.2软件和SHEsis网站进行连锁不平衡及单倍体分析。结果2个SNP位点共检测出3种基因型为GG、GA和AA,其基因型分布均符合Hardy-Weinberg平衡(P>0.05),同时在AMI组与对照组间差异无显著性(P>0.05)。多因素Logistic回归分析:增龄、高血压病、吸烟、低密度脂蛋白胆固醇(LDLC)和甘油三酯(TG)升高是AMI发病的独立危险因素(P<0.05),HDLC为保护因素(P<0.05)。在显性、隐性和加性3种不同遗传模式下进行Logistic回归分析发现,2个SNP位点与AMI发病无关联性。进行连锁不平衡和单倍型分析提示,该2个SNP位点处于同一个连锁不平衡区域(D′=1.000,r2=1.000),单倍型GG和AA均未增加AMI易感性(P>0.05)。结论GATA6基因启动区-493(rs144923558)G/A与-172(rs146748749)G/A两个SNP位点为完全连锁不平衡,其中GG为主要单倍型。该2个SNP位点及其单倍体型与AMI发病无相关性,但提供了GATA6基因启动区多态性的群体遗传学资料。Aim To investigate the relationship between single nucleotide polymorphism (SNP) of GATA6 gene promoter region-493 (rs144923558) G/A and -172 (rs146748749) G/A 2 sites and acute myocardial infarction (AMI) and their associated risk factors.Methods A case-control study was performed to collect 328 AMI patients and 344 normal controls (NC).Data were analyzed by polymerase chain reaction-restriction fragment length polymorphism technique combined with sequence alignment after DNA sequencing.After the Hardy-Weinberg balance test,the χ^2 test was used for correlation analysis;Logistic regression was used to analyze the relationship between multiple risk factors and two SNP loci and AMI incidence;linkage disequilibrium and haploid analysis was performed using Haplovview 4.2 software and SHEsis website.Results Three genotypes were detected in the two SNP loci,including GG,GA and AA.The genotype distribution was consistent with Hardy-Weinberg equilibrium (P>0.05),and there was no significant difference between the AMI group and the NC group(P>0.05).Multivariate Logistic regression analysis:age,hypertension,smoking,LDLC and TG were independent risk factors for AMI (P<0.05),and HDLC was protective factors (P<0.05).Logistic regression analysis in three different genetic models of dominant,recessive and additive suggests that the two SNP loci are not associated with the onset of AMI.Linkage disequilibrium and haplotype analysis indicated that the two SNP loci were in the same linkage disequilibrium region (D′=1.000,r2=1.000),and haplotypes GG and AA did not increase AMI susceptibility (P>0.05).Conclusions The GATA6 gene promoter-493 (rs144923558) G/A and -172 (rs146748749) G/A two SNPs are completely unbalanced,of which GG is the main haplotype.The two SNP loci and their haplotypes were not associated with the onset of AMI,but provided population genetics of the GATA6 gene promoter region polymorphism.

关 键 词：急性心肌梗死 基因启动区 单核苷酸多态性 危险因素 连锁不平衡 

分 类 号：R5[医药卫生—内科学]