CDKN2A／B基因三个单核苷酸多态性位点与冠心病的相关性研究

Relationship between single nucleotide polymorphism near gene CDKN2A/B and coronary artery disease

目的研究CDKN2A／B基因邻近的rs2383206、rs10757274、rs10757278三个位点的单核苷酸多态性（SNP），探讨其与冠心病的发病及冠状动脉病变程度的相关性。方法采用聚合酶链式反应（PCR）扩增CDKN2A／B基因邻近rs2383206、rs10757274、rs10757278三个SNP位点的核苷酸片段，进行多态性分型并分析其与冠心病发病的相关性，对冠心病患者冠脉造影结果进行Gensini积分评定，分析单核苷酸多态性分型与Gensini积分的关系。结果CDKN2A／B基因邻近的3个SNP位点rs2383206、rs10757274、rs10757278的AG／GG基因型分布频率均高于对照组（P〈0．05），G等位基因分布频率高于对照组（P〈0．05）。经校正混杂因素的影响后，与AA纯合子相比rs2383206、rs10757274、rs10757278的AG／GG基因型具有显著增加冠心病风险的效应校正比值比（OR）分别为1．492，1．915，1．866。冠心病组3个SNP位点AG／GG基因型冠脉Gensini积分均高于AA基因型（P〈0．05）。结论CDKN2A／B基因的rs2383206、rs10757274、rs10757278三个单核苷酸多态性位点是昆明地区汉族冠心病发生的易感位点，且与冠状动脉病变的严重程度呈正相关。

Objective To investigate single nucleotide polymorphism （SNP） of rs2383206, rs10757274 and rs10757278 on CDKN2A/B, and study the relationship between SNP and severity of coronary artery disease. Methods PCR-SNP stream technology was applied to determine rs2383206, rs10757274 and rs10757278 neighboring gene CDKN2A/B, in the mean time Gensini score was used to evaluate patients with coronary artery disease. Statistical analysis was done. Results The frequencies of AG/GG genotype of rs2383206, rs10757274 and rs 10757278 gene in coronary artery disease group were significantly higher than those in control group （P 〈 0.05）, so did G allele frequencies （P〈 0.05）. After adjusting for confounders, compared with AA homozygote, AG/GG genotypes of rs2383206, rs10757274 and rs 10757278 were associated with a remarkable increased risk of coronary artery disease （OR = 1.492, 1.915, 1.866）. In coronary artery disease group, for those 3 SNP, Gensini scores of patients with AG/GG genotypes were higher than those with AA genotype （P 〈 0.05）. Conclusion SNP of rs2383206, rs10757274 and rs10757278 are the susceptible loci for coronary artery disease in Kunming Hans, which is positively related to the severity of coronary artery disease.