CYP2A6 genetic polymorphism and its relation to risk of smoking dependence in male Iranians

Nicotine is the psychoactive substance responsible for establishing and maintaining smoking dependence. CYP2A6 is the primary enzyme that inactivates nicotine to cotinine. Genetic variation in CYP2A6 accounts for some of the inter-individual variability in nicotine metabolism and has been indicated to influence smoking behavior and dependence. Therefore, the aim of this study was to examine whether there is a relationship between CYP2A6 genetic polymorphism and smoking dependence in an Iranian population. We assessed 118 male non-smokers (1-99 cigarette/ lifetime) and 133 dependent current smokers for demographic, cigarette use history and DSM-IV dependence. CYP2A6 alleles associated with decreased nicotine metabolism (* 2, *4, or *9 allele) were determined using allele-specific nested PCR. Genotypes were grouped into slow metabolizers (one or two copies of *2 or *4, or two *9 alleles), intermediate (one *9 allele), and normal (have no copies of *2, *4, or *9 alleles). Intermediate nicotine metabolizers were at higher risk for becoming a dependent smoker odd ratio (OR = 3.71; p=0.009). Slow metabolizers had a significantly lower age of first smoking compared to normal and intermediate metabolizers (p = 0.037). Cigarette consumption and the degree of smoking dependence were not significantly different among smokers with different CYP2A6 genotypes. In Iranian population, the risk for becoming a dependent smokers increases with genotypes for intermediate metabolism of nicotine and slow nicotine metabolizers experience smoking in lower ages. These findings increase our understanding of the effect of CYP2A6 genotypes on smoking dependence in Iranian population and may help us to develop new strategies for quitting smoking.