Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population

Abstract

Several studies have reported that polymorphisms on chromosome 9p21.3, near the CDKN2A/2B gene, are strongly associated with increased susceptibility to abdominal aortic aneurysm (AAA). However, no convincing data has been reported on a relationship between AAA and these variants in the Chinese Han population. The aim of this study was to evaluate the role of rs10757278 and rs1333049 in determining genetic susceptibility to AAA. A total of 155 AAA patients and 310 controls, comparable in age and gender, were enrolled in this study. DNA samples were genotyped for rs10757278 and rs1333049 using the MassArray system. The association between these two single nucleotide polymorphisms and AAAs was tested using multivariate logistic regression. Stratified analysis was also performed by clinical and laboratory features. Single nucleotide polymorphisms rs10757278 and rs1333049 were significantly associated with increased risk of AAA. The frequencies of rs10757278-G and rs1333049-C in AAA patients were significantly higher than in control subjects (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.11-2.11; P = .01, and OR, 1.48; 95% CI, 1.07-2.05; P = .02). Multiple logistic regression analysis indicated that, after adjusting for smoking habits, drinking habits, and histories of other chronic diseases, homozygosity of the risk allele for rs10758278-G and rs1333049-C also increased the likelihood of AAA (OR, 2.31; 95% CI, 1.22-4.36, and OR, 2.14; 95% CI, 1.13-4.05). The frequency of the GC haplotype was significantly higher in AAA patients than in control subjects (OR, 1.44; P = .038). Stratification analysis of clinical and laboratory features revealed no association between polymorphisms and aortic diameters in AAA patients. There was a significantly high frequency of the rs10757278 GG genotype in AAA patients with high serum total homocysteine compared with those control subjects with high serum total homocysteine (OR, 2.71; 95% CI, 1.12-6.58; P = .03) indicating that the genotype GG of rs10757278 might interact with the homocysteine biological pathway to stimulate the presence of AAA. Present data demonstrate that rs10757278 and rs1333049 on chromosome 9p21.3 are significantly associated with increased risk of AAA in the Chinese population and emphasize the need to further study the role of these markers in AAA.