This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein β3-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 × 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).

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Journal The Pharmacogenomics Journal
Schelleman, H, Klungel, O.H, Witteman, J.C.M, Breteler, M.M.B, Hofman, A, Tikka-Kleemola, P, … Stricker, B.H.Ch. (2007). Diuretic-gene interaction and the risk of myocardial infarction and stroke. The Pharmacogenomics Journal, 7(5), 346–352. doi:10.1038/sj.tpj.6500428