2型糖尿病人群CDKN2A／B基因多态性与冠心病风险的相关性研究

目的观察T2DM人群细胞周期蛋白依赖激酶抑制基因2A／B（CDKN2A／B）基因多态性是否与冠心病风险相关，以早期筛查DM人群中冠心病的高危人群。方法对我院因胸痛症状行冠脉造影或冠脉CT检查的T2DM患者，根据冠脉造影或冠脉CT结果分为冠心病组及非冠心病组。冠心病组共220例，非冠心病组共89例。根据Hapmap数据库选取CDKN2A／B共7个单倍型标记的单核苷酸多态性（SNP）：CDKN2Ars2811708（G〉T）、rs3088440（A〉G）和rs3731239（C〉T），CDKN2Brs3217986（A〉C）、rs1063192（C〉T）、rs2285327（A〉G）和rs3217992（A〉G）。对所有个体进行PCR扩增并通过RFLP或基因测序方法读取个体的基因型。结果在T2DM人群中，冠心病组中cDKN2Ars2811708的次要等位基因T频率（26．4％）显著高于非冠心病组（17．4％）（P〈0．05），基因型分布在两组问存在显著性差异（P〈0．05），G／T基因型携带者较G／G基因型携带者发生冠心病的风险显著增加（P（0．05），在校正心血管其他风险因素（如性别、年龄、BMI、DM病程、高血压病病史、脂代谢异常病史、吸烟史）后，这种相关性仍然存在（P〈0．01）。结论T2DM人群中，CDKN2A／B基因单核苷酸多态性可能与冠心病的风险相关。

Genetic variation in cyclin dependent kinase inhibitor 2A/2B(CDKN2A/B) is associated with the risk of coronary artery disease in Chinese type 2 diabetes

Objective To investigate the association of cyclin dependent kinase inhibitor 2A/2B （CDKN2A/B） polymorphisms with the risk of coronary artery disease in type 2 diabetics in China. Methods Of total 309 subjects with type 2 diabetes,220 individuals with coronary artery disease as cases （CAD） and 89 controls （Non-CAD）were studied. From the Hapmap CHB database, we selected 7 haplotype-tagging single nucleotide polymorphisms （SNPs） in CDKN2A/B genes ： CDKN2A rs2811708 （G〉 T）, rs3088440（A〉G）and rs3731239（C〉T） ;CDKN2B rs3217986（A〉C）, rs1063192（C〉T）, rs2285327 （A〉G）and rs3217992（A〉G）. All the subjects for the 7 SNPs were genotyped by the polyrnerase chain reaction- restriction fragment length polymorphism（PCR-RFLP）assay or by direct DNA-sequencing. Results In Chinese type 2 diabetic patients, allelic frequency of minor allele T at rs2811708 was higher in CAD group（26.4%）than in non-CAD group（17. 4%）（OR= 1. 698, 95%CI 1. 092～2. 640, P= 0. 019）. Genotypic frequency at rs2811708 was associated with the risk of CAD in type 2 diabetics（P= 0. 028）. The carriers of genotype G/T had the increased risk of CAD compared to those of genotype G/G（OR= 2. 074, 95%CI 1. 194--3. 601, P= 0. 010）, and the association was consistent after adjustment for the other known risk factors of cardiovascular disease （adjusted OR = 2. 503,95% CI 1. 298 - 4. 825, P = 0. 006）. Conclusions Genetic variation in cyclin dependent kinase inhibitor 2A/2B（CDKN2A/B）genes is associated with cardiovascular risk in Chinese type 2 diabetics.