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

GONG Ming; LIU Ou; WANG Xiao-long; LIU Yu-yong; ZHENG Tie; LI Hai-yang; ZHANG Hong-jia

doi:10.3760/cma.j.issn.1673-4777.2011.s2.022

Abstract：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.