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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]

PMID: 31241144

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Project description:BackgroundAmerican Indian/Alaska Native (AI/AN) populations have been disproportionately affected by chronic respiratory diseases for reasons incompletely understood. Past research into disease disparity using population-based surveys mostly focused on state-specific factors. The present study investigates the independent contributions of AI/AN racial status and other socioeconomic/demographic variables to chronic respiratory disease disparity in an 11-state region with historically high AI/AN representation. Using data from the Behavioral Risk Factor Surveillance System (BRFSS) spanning years 2011-2018, this work provides an updated assessment of disease disparity and potential determinants of respiratory health in AI/AN populations.MethodsThis cross-sectional study used data from the BRFSS survey, 2011-2018. The study population included AI/AN and non-Hispanic white individuals resident in 11 states with increased proportion of AI/AN individuals. The yearly number of respondents averaged 75,029 (62878-87,350) which included approximately 5% AI/AN respondents (4.5-6.3%). We compared the yearly adjusted prevalence for chronic respiratory disease, where disease status was defined by self-reported history of having asthma and/or chronic obstructive pulmonary disease (COPD). Multivariable logistic regression was performed to determine if being AI/AN was independently associated with chronic respiratory disease. Covariates included demographic (age, sex), socioeconomic (marital status, education level, annual household income), and behavioral (smoking, weight morbidity) variables.ResultsThe AI/AN population consistently displayed higher adjusted prevalence of chronic respiratory disease compared to the non-Hispanic white population. However, the AI/AN race/ethnicity characteristic was not independently associated with chronic respiratory disease (OR, 0.93; 95% CI, 0.79-1.10 in 2017). In contrast, indicators of low socioeconomic status such as annual household income of <$10,000 (OR, 2.02; 95% CI, 1.64-2.49 in 2017) and having less than high school education (OR, 1.37; 95% CI, 1.16-1.63 in 2017) were positively associated with disease. These trends persisted for all years analyzed.ConclusionsThis study highlighted that AI/AN socioeconomic burdens are key determinants of chronic respiratory disease, in addition to well-established risk factors such as smoking and weight morbidity. Disease disparity experienced by the AI/AN population is therefore likely a symptom of disproportionate socioeconomic challenges they face. Further promotion of public health and social service efforts may be able to improve AI/AN health and decrease this disease disparity.

Project description:BackgroundAmerican Indians and Alaska Native (AI/AN) populations experience significant health disparities compared to non-Hispanic white populations. Cardiovascular disease and related risk factors are increasingly recognized as growing indicators of global health disparities. However, comparative reports on disparities among this constellation of diseases for AI/AN populations have not been systematically reviewed.ObjectivesWe performed a literature review on the prevalence of diabetes, metabolic syndrome, dyslipidemia, obesity, hypertension, and cardiovascular disease; and associated morbidity and mortality among AI/AN.Data sourcesA total of 203 articles were reviewed, of which 31 met study criteria for inclusion. Searches were performed on PUBMED, MEDLINE, the CDC MMWR, and the Indian Health Services.Study eligibility criteriaPublished literature that were published within the last fifteen years and provided direct comparisons between AI/AN to non-AI/AN populations were included.Study appraisal and synthesis methodsWe abstracted data on study design, data source, AI/AN population, comparison group, and. outcome measures. A descriptive synthesis of primary findings is included.ResultsRates of obesity, diabetes, cardiovascular disease, and metabolic syndrome are clearly higher for AI/AN populations. Hypertension and hyperlipidemia differences are more equivocal. Our analysis also revealed that there are likely regional and gender differences in the degree of disparities observed.LimitationsStudies using BRFSS telephone surveys administered in English may underestimate disparities. Many AI/AN do not have telephones and/or speak English. Regional variability makes national surveys difficult to interpret. Finally, studies using self-reported data may not be accurate.Conclusions and implications of key findingsProfound health disparities in cardiovascular diseases and associated risk factors for AI/AN populations persist, perhaps due to low socioeconomic status and access to quality healthcare. Successful programs will address social determinants and increase healthcare access. Community-based outreach to bring health services to the most vulnerable may also be very helpful in this effort.Systematic review registration numberN/A.

Dataset Information

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

Publications

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

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