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This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.

Original publication

DOI

10.1038/sj.tpj.6500493

Type

Journal article

Journal

The pharmacogenomics journal

Publication Date

12/2008

Volume

8

Pages

400 - 407

Addresses

Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands.

Keywords

Humans, Myocardial Infarction, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Risk Factors, Renin-Angiotensin System, Polymorphism, Genetic, Aged, Middle Aged, Female, Male, Stroke