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