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This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein beta3-subunit (GNB3) rs2301339 polymorphism modifies the risk of myocardial infarction (MI) or stroke. Data were used from the Rotterdam Study. The drug-gene interaction was determined with a Cox proportional hazard model with adjustment for each drug class as time-dependent covariates. The risk of MI in current users of low-ceiling diuretics with one or two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to the expected joint effect of the W-allele and low-ceiling diuretics on a multiplicative scale (1.04 x 0.90=0.94) (synergy index (SI):0.99; 95% confidence interval (CI): 0.43-2.27). No drug-gene interaction was found on the risk of stroke (SI:0.66; 95% CI:0.43-1.27). In addition, a trend towards an interaction was found between current use and the GNB3 rs230119 G/A polymorphism on the risk of MI (SI: 0.51; 95% CI: 0.23-1.15), whereas no interaction on the risk of stroke was found (SI: 0.84; 95% CI: 0.46-1.56).

Original publication

DOI

10.1038/sj.tpj.6500428

Type

Journal article

Journal

The pharmacogenomics journal

Publication Date

10/2007

Volume

7

Pages

346 - 352

Addresses

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

Keywords

Humans, Myocardial Infarction, Hypertension, Genetic Predisposition to Disease, Heterotrimeric GTP-Binding Proteins, Calmodulin-Binding Proteins, Diuretics, Population Surveillance, Proportional Hazards Models, Risk Assessment, Risk Factors, Follow-Up Studies, Prospective Studies, Gene Frequency, Polymorphism, Genetic, Time Factors, Aged, Middle Aged, Netherlands, Female, Male, Stroke