A meta-analysis of the angiotensin-converting enzyme gene polymorphism and restenosis after percutaneous transluminal coronary revascularization: evidence for publication bias

BACKGROUND: The insertion/deletion polymorphism of the gene encoding angiotensin-converting enzyme is a controversial risk factor for restenosis after percutaneous transluminal coronary revascularization in patients. Genetic association studies addressing this issue are frequently hampered by insufficient power. Therefore, we conducted a meta-analysis of this association, taking into account the possibility of publication bias. METHODS: We used the MEDLINE database and reviewed citations in relevant articles to identify 12 studies. Information on the design of the studies, the detailed genotype distribution, the angiographic follow-up rate, and the restenosis rate were categorized by use of a standardized protocol. RESULTS: Overall, DD (deletion-deletion) homozygotes had a higher restenosis risk than II (insertion-insertion) carriers (odds ratio 1.22, 95% CI 1.04-1.44, P <.05). However, the published studies were significantly heterogeneous, especially those addressing in-stent restenosis. Smaller studies tended to have positive results more frequently, which is characteristic of publication bias. Correcting for publication bias, we estimated the odds ratio to be 1.15 (95% CI 0.98-1.32, not significant). None of the published studies met all rules of genetic epidemiology. CONCLUSION: We conclude that a clinically significant association of the angiotensin-converting enzyme polymorphism with restenosis after percutaneous transluminal coronary revascularization in patients is unlikely. This meta-analysis provides evidence that the pooled estimate based on published literature, which favors an association, is distorted by publication bias. Hence, screening for this mutation in clinical practice is not justified. Future research should preferentially focus on gene-gene interaction and comply with the rules of genetic epidemiology