Angiotensin II type-I receptor and ACE polymorphisms and risk of myocardial infarction in men and women


Department of Epidemiology and Public Health (F. Kee), Belfast Monica Project (E. McCrum, A. E. Evans) and Department of Medicine (D. McMaster), Queen's University of Belfast, Belfast, Northern Ireland; Glasgow MONICA Project, Glasgow, Scotland (C. Morrison); INSERM U525, Paris, France (O. Poirier, C. Mallet, V. Nicaud); Institut Pasteur, Lille, France (J. Dallongeville).Correspondence to: Professor Frank Kee, Department of Epidemiology and Public Health, Queen's University of Belfast, Mulhouse Building, Grosvenor Rd, Belfast, Northern Ireland, BT12 6BJ. Tel.: +44–28–9089–4614; fax: +44–28–902321907; e-mail:


Findings relating an association between an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene and myocardial infarction (MI) have been mixed. While other loci, such as the angiotensin II type-I receptor (AT1R), may modulate risk, few studies have adequately documented the risk in women. We aimed to study whether the findings in respect of ACE and AT1R in UK men were borne out in women.

Cases of MI (305 women, 391 men) in Belfast and Glasgow have been compared to controls (291 women, 356 men). These new samples augment the original men (200 cases, 181 controls) included from Belfast in the ECTIM study.

Results Among men, the odds ratio for MI for ACE (DD vs. ID + II) was 1·03 (0·79, 1·34) and among women, 0·69 (0·47, 1·01). This heterogeneity between the risks in men and women was significant in Glasgow (P = 0·02). Among men and women the odds ratio for MI for AT1R (CC vs. AC + AA) was 1·02 (0·71, 1·47). There was a small gradient in risk, such that the odds ratio for DD genotype was 0·86 (0·63, 1·17) among subjects homozygous for the common AT1R alelle (AA): 0·94 (0·67, 1·30) among heterozygotes and 1·21 (0·53, 2·77) among CC subjects; but this interaction was not statistically significant.

Some of the contradictory findings concerning the ACE polymorphism and the risk of MI may be due to heterogeneity in the risk between men and women. The AT1R1196 polymorphism is not an independent risk factor for MI in either sex.