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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




Journal article


Eur J Hum Genet

Publication Date





478 - 484


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