Abstract
Angiotensinogen is an essential component of the renin-angiotensin system. ACE-inhibitors and β-blockers both have a direct influence on this system. To investigate whether the association between use of ACE-inhibitors or β-blockers and the risk of myocardial infarction (MI) or stroke is modified by the T-allele of the angiotensinogen M235T polymorphism. In this study, 4097 subjects with hypertension , aged 55 years and older, were included from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, from July 1, 1991 onwards. Follow-up ended at the diagnosis date of MI, stroke, death, or the end of the study period (January 1, 2002). The drug–gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model with adjustments for each drug class as time-dependent covariates. The risk of MI was increased in current use of ACE-inhibitors with the MT or TT genotype compared to ACE-inhibitors with the MM genotype (Synergy Index (SI): 4.00; 95% CI: 1.32–12.11). A significant drug–gene interaction was not found on the risk of stroke (SI: 1.83; 95% CI: 0.95–3.54) in ACE-inhibitor users or between current use of β-blockers and the AGT M235T polymorphism on the risk of MI or stroke. ACE-inhibitor users with at least one copy of the 235T-allele of the AGT gene might have an increased risk of MI and stroke.
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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 greatly acknowledged.
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Schelleman, H., Klungel, O., Witteman, J. et al. Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or β-blockers. Eur J Hum Genet 15, 478–484 (2007). https://doi.org/10.1038/sj.ejhg.5201789
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DOI: https://doi.org/10.1038/sj.ejhg.5201789
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