Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction

• Published in: Journal of medical genetics Vol. 41; no. 10; pp. 758 - 762
• Main Authors: Cornelis, M C, El-Sohemy, A, Campos, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.10.2004; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: 95% CI; 95% confidence intervals; Atherosclerosis; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular disease; CHD; Coronary heart disease; Costa Rica; CYP1A1; CYP1A2; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A2 - genetics; DNA damage; Enzymes; Female; General aspects. Genetic counseling; Genetic Predisposition to Disease - genetics; Genotype; Heart; Heart attacks; Hospitals; Humans; Male; Medical genetics; Medical sciences; Middle Aged; myocardial infarction; Myocardial Infarction - genetics; Myocarditis. Cardiomyopathies; odds ratios; Original; Polycyclic aromatic hydrocarbons; Polymorphism; Polymorphism, Genetic - genetics; Questionnaires; restriction-fragment length polymorphism; RFLP; Smoking; Smoking - adverse effects; Socioeconomic factors; Thermal cycling; Tobacco smoke; Costa Rica; Canada; Human; Myocardial infarction; Heart disease; Risk factor; Cardiovascular disease; Genetics; Risk; Increase; Myocardial disease; Polymorphism
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2004.022012

Background: There is growing evidence that DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). In order to bind to DNA many mutagens require metabolic activation by cytochrome P450 (CYP) 1A1 or CYP1A2. The objective of this study was to determine the effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and whether smoking interacts with genotype to modify risk. Methods: Subjects (n = 873) with a first acute non-fatal MI and population based controls (n = 932) living in Costa Rica, matched for age, sex, and area of residence, were genotyped for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)-PCR, and smoking status was determined by questionnaire. Results: After adjusting for matching variables and potential confounders, no association was observed between CYP1A1 genotype and risk of MI. Compared to individuals with the high inducibility CYP1A2*1A/*1A genotype, the adjusted odds ratio and 95% confidence intervals for risk of MI were 1.19 (0.97 to 1.47) for the *1A/*1F genotype and 1.55 (1.10 to 2.18) for the *1F/*1F genotype. No significant interactions were observed between smoking and either CYP1A1 or CYP1A2 genotype. Conclusions: The low inducibility genotype for CYP1A2 was associated with an increased risk of MI. This effect was independent of smoking status and suggests that a substrate of CYP1A2 that is detoxified rather than activated may play a role in CHD.