Angiotensinogen M235T polymorphism and the risk of myocardial infarction and stroke among hypertensive patients on ACE-inhibitors or beta-blockers.
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.
Schelleman
Hedi
H
Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Klungel
Olaf H
OH
Witteman
Jacqueline C M
JC
Breteler
Monique M B
MM
Yazdanpanah
Moygan
M
Danser
A H Jan
AH
Hofman
Albert
A
van Duijn
Cornelia M
CM
de Boer
Anthonius
A
Stricker
Bruno H Ch
BH
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000808:Angiotensinogen / Q000235:genetics*; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen