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Drug-Gene Interactions between Genetic Polymorphisms and Antihypertensive Therapy

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Abstract

Genetic factors may influence the response to antihypertensive medication. A number of studies have investigated genetic polymorphisms as determinants of cardiovascular response to antihypertensive drug therapy. In most candidate gene studies, no such drug-gene interactions were found. However, there is observational evidence that hypertensive patients with the 460W allele of the α-adducin gene have a lower risk of myocardial infarction and stroke when treated with diuretics compared with other antihypertensive therapies. With regard to blood pressure response, interactions were found between genetic polymorphisms for endothelial nitric oxide synthase and diuretics, the α-adducin gene and diuretics, the α-subunit of G protein and β-adrenoceptor antagonists, and the ACE gene and angiotensin II type 1 (AT1) receptor antagonists. Other studies found an interaction between ACE inhibitors and the ACE insertion/deletion (I/D) polymorphism, which resulted in differences in AT1 receptor mRNA expression, left ventricular hypertrophy and arterial stiffness between different genetic variants. Also, drug-gene interactions between calcium channel antagonists and ACE I/D polymorphism regarding arterial stiffness have been reported. Unfortunately, the quality of these studies is quite variable. Given the methodological problems, the results from the candidate gene studies are still inconclusive and further research is necessary.

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Acknowledgements

Preparation of this article was financially supported by the Netherlands Heart Foundation, grant number: 2001.064. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, Erasmus MC, 3000 DR, Rotterdam, PO Box 1738, The Netherlands

    Hedi Schelleman,  Bruno H. Ch. Stricker & Cornelia M. van Duijn

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

    Hedi Schelleman, Anthonius de Boer & Olaf H. Klungel

  3. Department of Internal Medicine, University Hospital of Maastricht and Cardiovascular Research Institute Maastricht (CARIM), Maastricht, The Netherlands

    Abraham A. Kroon

  4. Centre for Prevention and Health Services Research, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    Monique W. M. Verschuren

  5. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, USA

    Bruce M. Psaty

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Schelleman, H., Stricker, B.H.C., de Boer, A. et al. Drug-Gene Interactions between Genetic Polymorphisms and Antihypertensive Therapy. Drugs 64, 1801–1816 (2004). https://doi.org/10.2165/00003495-200464160-00006

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