CYP2A6 genetic polymorphisms and correlation with smoking status in Brazilians

We investigated polymorphisms of cytochrome P450 2A6 ( CYP2A6) and its association with smoking habits in 412 healthy Brazilians, self- recognized as white ( n = 147), black ( n = 123) and intermediate ( n = 142), and classified as smokers ( n = 205, including 61 ex- smokers) and nonsmokers ( n = 207). The frequencies of the variant alleles CYP2A6* 1B, CYP2A6* 2, CYP2A6* 4 and CYP2A6* 9 in the overall study population were 29.9, 1.7, 0.5 and 5.7%, respectively. Significant differences in the CYP2A6 allelic distribution were observed across the three population subgroups. There was a statistically significant trend for decreasing frequency of CYP2A6* 1B from white to intermediate and to black persons. An association between CYP2A6 genotype and smoking dependence was detected, which could not be explained by the expected phenotypic activity of CYP2A6. In white and intermediate persons, the odds ratio ( OR) of being smokers vs nonsmokers was 0.07 ( 95% CI 0.02 - 0.20; P < 0.001) and 0.27 ( 95% CI 0.12 - 0.61; P < 0.001), respectively, for genotypes including allele CYP2A6* 1B, as compared to wild- type homozygous. In contrast, the corresponding OR in black Brazilians was 1.34 ( 95% CI 0.57 - 3.17; P = 0.46). These data suggest that the CYP2A6* 1B is associated with smoking dependence in white and intermediate, but not black Brazilians.