Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction.
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.
Cornelis
M C
MC
Department of Nutritional Sciences, University of Toronto, Ontario, Canada M5S 3E2.
El-Sohemy
A
A
Campos
H
H
D003364:Costa Rica; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2