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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Journal European Journal of Human Genetics
Schelleman, H, Klungel, O.H, Witteman, J.C.M, Breteler, M.M.B, Yazdanpanah, M, Danser, A.H.J, … Stricker, B.H.Ch. (2007). Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or β-blockers. European Journal of Human Genetics, 15(4), 478–484. doi:10.1038/sj.ejhg.5201789