Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm.

Abstract

Abdominal aortic aneurysm (AAA) formation involves an inflammatory and proteolytic process. Previous studies suggest that AAA is a multifactorial disease with a strong genetic background. This study evaluated the role of seven important functional single nucleotide polymorphisms (SNPs) in AAA. This was a case-control study of two independent populations: 397 AAA patients (mean aortic diameter, 6.2 ± 1.4 cm) and 393 controls (mean diameter, 2.4 ± .2 cm) recruited from Greece (the main cohort), and 400 patients (mean diameter: 5.4 ± 1 cm) and 400 controls (mean diameter, 2.4 ± .6 cm) recruited from the United Kingdom (replication cohort). The functional SNPs analyzed were rs3025058, rs3918242, rs2276109, rs1801133, rs1799752, rs1799983, and rs16874954. These regulate the following enzymes: matrix metalloproteinases (MMPs), angiotensin-converting enzyme, endothelial nitric oxide synthase, methylenetetrahydrofolate reductase (MTHFR), and platelet-activating factor acetylhydrolase or lipoprotein-associated phospholipase A2. Genotype distributions (univariate analyses) did not differ significantly between cases and controls in the main or the replication cohort, with the exception of the MMP-3 rs3025058 SNP, where differences were borderline significant (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.02-1.97; P = .04) in the replication cohort. Adjusted analyses for age, sex, smoking, hypertension, and hypercholesterolemia disclosed no differences in either cohort. For SNPs that had previously been associated with AAA presence, meta-analysis of currently available data together with the two study cohorts disclosed positive associations for the MMP-3 rs3025058 (OR, 1.15; 95% CI, 1.06-1.25; P = .0009) and MTHFR rs1801133 (OR, 1.07; 95% CI, 1.02-1.12; P = .0088). The SNPs included in this analysis were not associated with AAA presence in either study population. However, meta-analysis of the currently available data disclosed a positive association for MMP-3 rs3025058 and MTHFR rs1801133.