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Diuretic–gene interaction and the risk of myocardial infarction and stroke

The Pharmacogenomics Journal volume 7, pages 346–352 (2007)Cite this article

Abstract

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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Acknowledgements

The Netherlands Heart Foundation financially supported this study, grant number: 2001.064. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), the Municipality of Rotterdam, and the Centre for Medical Systems Biology (CMSB). The contributions of the general practitioners and pharmacists of the Ommoord district to the Rotterdam Study are gratefully acknowledged.

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Authors and Affiliations

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

    H Schelleman, J C M Witteman, M M B Breteler, A Hofman, C M van Duijn & B H Ch Stricker

  2. Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands

    H Schelleman, O H Klungel & A de Boer

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  1. H Schelleman
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  2. O H Klungel
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  3. J C M Witteman
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  4. M M B Breteler
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  5. A Hofman
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  6. C M van Duijn
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  7. A de Boer
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  8. B H Ch Stricker
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Correspondence to B H Ch Stricker.

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None declared.

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Schelleman, H., Klungel, O., Witteman, J. et al. Diuretic–gene interaction and the risk of myocardial infarction and stroke. Pharmacogenomics J 7, 346–352 (2007). https://doi.org/10.1038/sj.tpj.6500428

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  • DOI: https://doi.org/10.1038/sj.tpj.6500428

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