Candidate Gene Association Studies in Abdominal Aortic Aneurysm Disease: A Review and Meta-Analysis

BackgroundCandidate gene analysis has been frequently used in attempts to understand the pathological processes involved in many aspects of AAA disease.MethodsThis paper sets out a systems approach to reviewing AAA candidate gene analysis studies, whilst, explaining the key principles and design limitations of this universally applied technique. In addition we have performed a meta-analysis of six gene polymorphisms (ACE I/D, MTHFR+677C>T, MMP9−1562C>T, Il-1Beta/3953C>T, eNOS 4a/4b & TIMP1/+434C>T) reported in multiple case control studies.Results and conclusionsThree of these polymorphisms were associated with a significant risk of AAA, ACE RR 1.33 [95% CI 1.20–1.48], MTHFR RR 1.14 [1.08–1.21] and MMP9 RR 1.09 [1.01–1.18]. These differences have been previously reported as equivocal, within a context of contradictory studies and as such this meta-analysis provides new evidence for their involvement in AAA disease. The plausibility of these findings is discussed within the context of a systems approach to the pathology of AAA disease