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Interactions between five candidate genes and antihypertensive drug therapy on blood pressure

The Pharmacogenomics Journal volume 6, pages 22–26 (2006)Cite this article

Abstract

Despite the availability of effective antihypertensive drugs, there is a large variation in response to these drugs. This study investigates whether polymorphisms in the angiotensin converting enzyme (I/D), angiotensinogen (M235T), α-adducin (G460W), angiotensin II type 1 receptor (1166A/C), or G protein β3-subunit (825C/T) gene modify the mean difference in blood pressure levels among diuretics, β-blockers, or ACE-inhibitors users. Data were used from the Doetinchem Cohort Study, and blood pressure data were collected from GPs (1987–1997). A marginal generalized linear model (GEE) was used to assess the gene–drug interaction on the mean difference in systolic/diastolic blood pressure. In total, 625 hypertensive individuals were included with a total of 5262 measurements of blood pressure. Only the interaction between diuretic use and the GNB3 825C/T polymorphism was significant (C allele versus TT systolic blood pressure (SBP): 4.33 mmHg [95% CI: 0.14–8.54]). Thus, the mean SBP level among diuretic users may be modified by the GNB3 825C/T polymorphism.

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Acknowledgements

This study was financially supported by The Netherlands Heart Foundation, grant number: 2001.064; the Ministry of Health, Welfare and Sport of the Netherlands, and the National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

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Authors and Affiliations

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

    H Schelleman & B H Ch Stricker

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

    H Schelleman, A de Boer & O H Klungel

  3. Centre for Prevention and Health Service Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    W M M Verschuren

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

    A A Kroon & P W de Leeuw

  5. Division of Nutrition and Consumer Safety, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    D Kromhout

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  1. H Schelleman
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  2. B H Ch Stricker
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  3. W M M Verschuren
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  4. A de Boer
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  5. A A Kroon
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  6. P W de Leeuw
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  7. D Kromhout
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  8. O H Klungel
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Correspondence to O H Klungel.

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Schelleman, H., Stricker, B., Verschuren, W. et al. Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. Pharmacogenomics J 6, 22–26 (2006). https://doi.org/10.1038/sj.tpj.6500339

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  • DOI: https://doi.org/10.1038/sj.tpj.6500339

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