Candidate gene association studies in abdominal aortic aneurysm disease: A review and meta-analysis

Background. Candidate gene analysis has been frequently used in attempts to understand the pathological processes involved in many aspects of AAA disease. Methods. This 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 conclusions. Three 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. (C) 2007 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.