CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people.

Pharmacogenetics and Genomics
Matthew J BinningtonRachel F Tyndale

Abstract

Alaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward the increased risk. AN people (n=400) residing in the Bristol Bay region of South Western Alaska were recruited for a cross-sectional study on tobacco use. They were genotyped for CYP2A6*1X2A, *1X2B, *1B, *2, *4, *7, *8, *9, *10, *12, *17, *35 and CYP2B6*4, *6, *9 and provided plasma and urine samples for the measurement of nicotine and metabolites. CYP2A6 and CYP2B6 variant frequencies among the AN Yupik people (n=361) were significantly different from those in other ethnicities. Nicotine metabolism [as measured by the plasma and urinary ratio of metabolites trans-3'-hydroxycotinine to cotinine (3HC/COT)] was significantly associated with CYP2A6 (P<0.001), but not CYP2B6 genotype (P=0.95) when controlling for known covariates. It was noteworthy that the plasma 3HC/COT ratios were high in the entire Yupik people, and among the Yupik CYP2A6 wild-type participants, they were substantially...Continue Reading

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