The genetics of abdominal aortic aneurysms: a comprehensive meta-analysis involving eight candidate genes in over 16,700 patients

Abstract

Abdominal aortic aneurysms (AAAs) are thought to be multifactorial in etiology. A variety of susceptibility genes have been associated, but definitive conclusions have been difficult to draw and are partly hampered by the small number of patients in each study. We undertook a comprehensive meta-analysis on any gene that was investigated in a case-control model of AAA. A comprehensive, genetic meta-analysis of all genes investigated by using an allelic-association, case-control model in AAA was conducted. Electronic databases were searched through July 2009 for any candidate gene in AAA. Odds ratio (OR) and 95% confidence intervals (CIs) were determined for each gene-disease association by using fixed- and random-effect models. Twenty studies in 7 candidate genes were analysed among 16,748 individuals (i.e., 7891 patients and 8857 controls). Of the 8 genes studied, 5 genes were associated with AAA. The angiotensin-1 converting enzyme (ACE) insertion/deletion polymorphism (I/D) showed a significant association in both a dominant model (OR, 1.35; 95% CI, 1.17 to 1.56; P < 0.0001) and a recessive model (OR 1.24; 95% CI, 1.08 to 1.42; P < 0.00001). The pooled ORs for the C677T variant of 5,10-methyltetrahydrofolate reductase (MTHFR) were 1.34 (95% CI, 1.08 to 1.65; P = 0.007) for the dominant model and 1.16 (95% CI, 0.81 to 1.67; P = 0.41) for a recessive model. There was also significance in the dominant model of the angiotensin-1 receptor polymorphism (AT1R) A1166C (OR, 1.94; 95% CI, 1.66 to 2.28; P < 0.00001) and in the dominant (95% CI, 1.18 to 2.11; P = 0.002) and recessive (OR, 1.51; 95% CI, 1.13 to 2.02; P = 0.006) models of the interleukin-10 1082 polymorphism. The MMP-3 nt-1612 polymorphism was also significant in the dominant (OR, 1.4; 95% CI, 1.12 to 1.76; P = 0.003) and recessive (OR 1.3; 95% CI, 1.05 to 1.61; P = 0.02) models. In conclusion, there is a genetic basis to sporadic aortic aneurysms. Patients with the ACE/D and MTHFR/677T, AT1R/C, IL-10/A, and MMP-3 nt-1612 polymorphisms are at an increased risk of developing this condition.