候选基因单核苷酸多态性与胸主动脉夹层的遗传易感性分析

目的 探讨6个候选基因单核苷酸多态性位点与中国汉族人群胸主动脉夹层发病的相关性.方法 选取中国汉族人群的206例高血压合并胸主动脉夹层患者及180例原发性高血压病患者,收集样本外周血白细胞提取DNA,利用基质辅助激光解吸电离质谱方法对5个与甲硫氨酸代谢相关基因(RS819146、RS8003379、RS2853523、RS326118与RS3788205)及1个与细胞周期蛋白依赖酶抑制剂基因相关的单核苷酸多态性位点(RS1075727)进行基因分型.比较胸主动脉夹层组与高血压组之间基因多态性位点的基因型、等位基因频率.结果 胸主动脉夹层者组的男性比例要高于高血压组.RS819146、RS8003379、RS2853523、RS326118与RS3788205基因多态性位点其等位基因频率与基因型频率差异均无统计学意义.RS10757278的A等位基因频率在男性胸主动脉夹层患者中的比例(59.4％)要高于男性高血压组(47.2％),差异有统计学意义(P=0.010).此外,利用Logisitic回归校正心血管疾病发病相关危险因素(包括年龄、血压、糖尿病、血脂异常及吸烟),发现该基因多态性是男性胸主动脉夹层发病的独立危险因素[比值比(OR)=0.61,95％可信区间(CI) =0.42 ～0.89)].结论 与细胞周期蛋白依赖酶抑制剂基因相关的单核苷酸多态性位点A等位基因是中国男性汉族人群胸主动脉夹层发病的重要遗传易感因素.

The association of susceptibility of thoracic aortic dissections and single nucleotide polymorphism in candidate genes

Objective To determine whether six single nucleotide polymorphisms (SNP) in candidate genes confer significant susceptibility to thoracic aortic dissections (TAD) in a Chinese Han population.Methods Two hundred and six hypertensive patients with thoracic aortic dissection and 180 hypertensive patients without aortic dissection from the ethnic Chinese Han population were enrolled.Genomic DNAs were extracted from peripheral blood leucocytes.Five susceptibility SNPs in five genes involved in methionine metabolism(RS819146,RS8003379,RS2853523,RS326118 and RS3788205 ) and one SNP in the gene for cyclin-dependent kinase inhibitor( RS1075727 ) were genotyped using high-throughput matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry.The gene SNPs genotype and allele frequency were compared between hypertensive patients with aortic dissection and without.Results Male ratio of thoracic aortic dissection group washigher in that in the hypertensive group.RS819146,RS8003379,RS2853523,RS326118 and RS3788205 gene polymorphisms in the allele frequencies and genotype frequencies were not significantly different.The proportion of the A allele frequency of RS10757278 site in male patients with thoracic aortic dissection (59.4％) was higher than that in the male hypertension group (47.2％),the difference was statistically significant (P =0.010).In addition,with the multiple logistic regression analysis adjusted for traditional cardiovascular risk factors (sex,age,hypertension,dyslipidaemia,diabetes and smoking habit),this SNP resulted in an independent susceptibility factor for TAD in males[odds ratio (OR) 0.61,95％ confidence interval (CI) 0.42 to 0.89].Conclusion Our results suggest that the variant in the gene for cyclin-dependent kinase inhibitor is an important susceptibility locus for development of TAD in Chinese Han population.