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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.