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Interaction between polymorphisms in the renin–angiotensin–system and angiotensin-converting enzyme inhibitor or β-blocker use and the risk of myocardial infarction and stroke

The Pharmacogenomics Journal volume 8, pages 400–407 (2008)Cite this article

Abstract

This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or β-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug–gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14–0.70). No significant drug–gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44–1.52) or in β-blocker users. Also, no significant drug–gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.

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Abbreviations

ACE:

angiotensin-converting enzyme

AGTR1:

angiotensin receptor type 1

MI:

myocardial infarction

RAS:

renin–angiotensin–system

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Acknowledgements

This study was financially supported by The Netherlands Heart Foundation (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 greatly 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. Interaction between polymorphisms in the renin–angiotensin–system and angiotensin-converting enzyme inhibitor or β-blocker use and the risk of myocardial infarction and stroke. Pharmacogenomics J 8, 400–407 (2008). https://doi.org/10.1038/sj.tpj.6500493

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  • DOI: https://doi.org/10.1038/sj.tpj.6500493

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