Interaction between polymorphisms in the renin-angiotensin-system and angiotensin-converting enzyme inhibitor or beta-blocker use and the risk of myocardial infarction and stroke.
This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.
Schelleman
H
H
Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands.
Klungel
O H
OH
Witteman
J C M
JC
Breteler
M M B
MM
Hofman
A
A
van Duijn
C M
CM
de Boer
A
A
Stricker
B H Ch
BH
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000517:prevention & control; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000235:genetics* / Q000517:prevention & control
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors