Pharmacogenomics of nicotine metabolism: novel CYP2A6 and CYP2B6 genetic variation patterns in Alaska Native and American Indian populations.

 
TitlePharmacogenomics of nicotine metabolism: novel CYP2A6 and CYP2B6 genetic variation patterns in Alaska Native and American Indian populations.
Publication TypeJournal Article
Year of Publication2019
AuthorsClaw, KG, Beans, JA, Lee, S-B, Avey, JP, Stapleton, PA, Scherer, SE, El-Boraie, A, Tyndale, RF, Nickerson, DA, Dillard, DA, Thummel, KE, Robinson, RF
JournalNicotine Tob Res
Date Published2019 Jun 25
ISSN1469-994X
Abstract

INTRODUCTION: Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic (Pgx) 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 (e.g., 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 Pgx 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.

DOI10.1093/ntr/ntz105
Alternate JournalNicotine Tob. Res.
PubMed ID31241144