Papers

Angiotensin converting enzyme insertion or deletion polymorphism and coronary restenosis: meta-analysis of 16 studies

François Bonnici, Rhodes scholar, ^a Bernard Keavney, senior lecturer, ^b Rory Collins, professor of medicine and epidemiology, ^a John Danesh, professor of epidemiology and medicine. ^c

^a Clinial Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, ^b University Department of Cardiology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, ^c Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, Cambridge CB2 2SR

Correspondence to: J Danesh

Objective: To assess the association between genotype at the insertion or deletion polymorphism of the angiotensin converting enzyme gene and risk of coronary restenosis after percutaneous coronary intervention.
Design: Meta-analysis of studies before July 2001 that reported on these genotypes and risk of coronary restenosis after a percutaneous coronary intervention, with or without coronary stenting.
Results: 16 studies, involving 4631 patients undergoing a percutaneous coronary intervention, yielded 1683 patients with restenosis after a mean weighted follow up of 5.5 months. The combined odds ratio for restenosis in people with the DD genotype was 1.23 (99% confidence interval 1.03 to 1.46). When studies were grouped by size, however, the combined odds ratios for restenosis in people with the DD genotype were 1.94 (1.39 to 2.71) for studies with less than 100 cases, 1.33 (0.92 to 1.93) for studies with 100-200 cases, and 0.92 (0.72 to 1.18) for studies with more than 200 cases (trend P=0.02). Similarly, when studies were grouped by genotyping procedures, significantly larger odds ratios were found in the studies that did not conceal disease status from laboratory staff and in the studies that did not use a second polymerase chain reaction amplification to reduce genetic mistyping.
Conclusion: Compared with other studies, larger and more rigorous studies show a weaker association between the angiotensin converting enzyme gene DD genotype and restenosis. Publication bias or detection biases can produce artefactual associations at least as large as those that might be expected for common polymorphisms in complex diseases, suggesting the need for larger and more rigorous genetic epidemiological investigations than are now customary.

What is already known on this topic Restenosis after a percutaneous coronary intervention is one of the principal limitations of the technique Genotype at the angiotensin converting enzyme insertion or deletion polymorphism is proposed to be important in restenosis What this study adds Weaker associations between the angiotensin converting enzyme DD genotype and restenosis were found in larger and more rigorous studies than in other studies Publication bias or detection biases, or both, can produce artefactual associations at least as large as those that might be expected for common polymorphisms in complex diseases