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Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations.


ABSTRACT: INTRODUCTION:Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation. METHODS:Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations). RESULTS:Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup. CONCLUSIONS:Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations. IMPLICATIONS:Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy.

SUBMITTER: Claw KG 

PROVIDER: S-EPMC7249913 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations.

Claw Katrina G KG   Beans Julie A JA   Lee Seung-Been SB   Avey Jaedon P JP   Stapleton Patricia A PA   Scherer Steven E SE   El-Boraie Ahmed A   Tyndale Rachel F RF   Nickerson Deborah A DA   Dillard Denise A DA   Thummel Kenneth E KE   Robinson Renee F RF  

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20200501 6


<h4>Introduction</h4>Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation.<h4>Methods</h4>Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout A  ...[more]

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