Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Angiotensinogen is an essential component of the renin-angiotensin system. ACE-inhibitors and beta-blockers both have a direct influence on this system. To investigate whether the association between use of ACE-inhibitors or beta-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 beta-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.

Original publication

DOI

10.1038/sj.ejhg.5201789

Type

Journal article

Journal

European journal of human genetics : EJHG

Publication Date

04/2007

Volume

15

Pages

478 - 484

Addresses

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

Keywords

Humans, Myocardial Infarction, Hypertension, Genetic Predisposition to Disease, Angiotensinogen, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Risk Factors, Cohort Studies, Longitudinal Studies, Prospective Studies, Pharmacogenetics, Comorbidity, Renin-Angiotensin System, Polymorphism, Genetic, Aged, Aged, 80 and over, Middle Aged, Netherlands, Female, Male, Stroke