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.


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.
Thompson
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Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, 5 University Street, London WC1E 6JF, UK.
Drenos
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Hafez
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Humphries
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D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology / Q000235:genetics*; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D053583:Interleukin-1beta; D019715:Tissue Inhibitor of Metalloproteinase-1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A; D020780:Matrix Metalloproteinase 9