Pleiotropic effects of genotypes at rs10757274 locus of coronary heart disease susceptibility gene CDKN2B-AS1 on type 2 diabetes mellitus and hyperlipemia

目的 探讨冠心病易感基因CDKN2B-AS1位点rs10757274基因型对2型糖尿病、高脂血症及其合并症的多效性作用,为心脑血管疾病的遗传病因学研究提供新思路.方法 采用多病例组-对照没计,纳入北京大学第一医院2012年6月至2013年3月心内科入院的汉族冠心病患者1 158例为研究对象,其中非高脂血症的2型糖尿病患者242例(20.9％),非2型糖尿病的高脂血症患者306例(26.4％),2型糖尿病合并高脂血症204例(17.6％),对照组(不患2型糖尿病和高脂血症)406例(35.1％).对研究对象进行问卷调查、体格检查和生化指标测定.采用单碱基延伸技术和GenomeLab SNP基因分型系统(美国Beckman Coulter公司)进行基因分型.采用非条件logistic回归进行关联分析,调整年龄、性别、体质指数、吸烟、饮酒、高血压和心肌梗死.结果 与基因型GG相比,基因型GA/rs10757274(OR=2.43,95％ CI:1.58～3.74)与基因型AA/rs10757274(OR=2.64,95％ CI:1.62～4.30)会增加患2型糖尿病的风险;基因型GA/rs10757274(0R=2.25,95％CI:1.53～3.30)与基因型AA/rs10757274(OR=1.89,95％ CI:1.20～2.97)会增加高脂血症的风险;基因型GA/rs10757274(OR=1.86,95％CI:1.15～3.01)与基因型AA/rs10757274(0R=4.21,95％ CI:2.55～6.92)会增加2型糖尿病合并高脂血症的风险.结论 CDKN2B-AS1基因位点rs10757274基因型对2型糖尿病、高脂血症具有遗传多效性.Objective To explore the pleiotropic effects of genotypes at rs10757274 locus in coronary heart disease(CHD) susceptibility gene CDKN2B-ASI on type 2 diabetes mellitus (T2DM) and hyperlipemia and to provide the new idea for genetic etiology study of cardiovascular and cerebrovascular diseases.Methods In present hospital-based case-control study,1 158 CHD patients were the subjects,which included 242 T2DM without hyperlipemia cases (20.9％),306 non-T2DM with hyperlipemia cases (26.4％).204 T2DM with hyperlipemia cases (17.6％) and 406 controls (non-T2DM without hyperlipemia cases,35.1％).All subjects were Han people.The present study was performed by questionnaire,physical examination and biochemical test for all subjects.The single base prime extension genotyping technology and GenomeLab SNP stream genotyping system were used to conduct genotyping.Multivariate unconditional logistic regression analysis were utilize to analyzethe correlation with adjustments for age,sex,BMI,smoking,alcohol drinking,hypertension and myocardial infarction.Results As compared with genotype GG,genotype GA/rs10757274 (OR=2.43.95％CI:1.58-3.70) and genotype AA/rs10757274 (OR=2.64.95％CI:1.62-4.30) could increase the risk ofT2DM.Genotype GA/rs10757274 (OR=2.25.95％CI:1.53-3.30) and genotype AA/rs10757274 (OR=1.89.95％CI:1.20-2.97) could increase the risk of hyperlipemia.Genotype GA/rs10757274 (OR=1.86.95％CI:1.15-3.01) and genotype AA/rs10757274 (OR=4.21.95％CI:2.55-6.92) could increase the risk of T2DM with hyperlipemia.Conclusion There are the pleiotropic effects of genotypes at rs10757274 locus of ge CDKN2B-AS1 on T2DM and hyperlioemia.国家自然科学基金项目中国科技核心期刊(ISTIC)293-972