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

Claw, Katrina G.; Beans, Julie A.; Lee, Seung‐been; Avey, Jaedon P; Stapleton, Patricia; Scherer, Steven E.; El‐Boraie, Ahmed; Tyndale, Rachel F.; Nickerson, Deborah A.; Dillard, Denise A.; Thummel, Kenneth E.; Robinson, Renee

doi:10.1093/ntr/ntz105

Cited by 15 publications

(16 citation statements)

References 41 publications

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“…A Native American Research Center for Health led by one of our partners has extended the pharmacogenetic research focus to tobacco cessation treatment, with potential implications for improved clinical management (38,130). We have also explored interest in pharmacogenetics in the communities where we work (44,124).…”

Section: A New Venture: a Regional Pharmacogenomics Research Networkmentioning

confidence: 99%

Untitled

2021

Annu. Rev. Genom. Hum. Genet.

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Genomic information is poised to play an increasing role in clinical care, extending beyond highly penetrant genetic conditions to less penetrant genotypes and common disorders. But with this shift, the question of clinical utility becomes a major challenge. A collaborative effort is necessary to determine the information needed to evaluate different uses of genomic information and then acquire that information. Another challenge must also be addressed if that process is to provide equitable benefits: the lack of diversity of genomic data. Current genomic knowledge comes primarily from populations of European descent, which poses the risk that most of the human population will be shortchanged when health benefits of genomics emerge. These two challenges have defined my career as a geneticist and have taught me that solutions must start with dialogue across disciplinary and social divides.

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Section: A New Venture: a Regional Pharmacogenomics Research Networkmentioning

confidence: 99%

Untitled

2021

Annu. Rev. Genom. Hum. Genet.

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“…The CN, on the other hand, was beginning to think about the role of genetic research for its own community. While MB had participated in select genetic studies over the years ( Claw et al, 2020 ; Khan et al, 2018 ; Fohner et al, 2015 ; Woodahl et al, 2014 ), many questions remain about perceptions of genetic research that had never been asked of its community before the deliberation. Findings from this deliberation have been disseminated to the appropriate tribal authorities for review and consideration ( Reedy et al, 2020b ).…”

Section: Balancing Local Priorities and Collective Goalsmentioning

confidence: 99%

Power Sharing, Capacity Building, and Evolving Roles in ELSI: The Center for the Ethics of Indigenous Genomic Research

Blanchard¹,

Hiratsuka²,

Beans³

et al. 2020

Collaborations: A Journal of Community-Based Research and Practice

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Persistent, unresolved issues stemming from a legacy of scientific exploitation and bio-colonialism have kept many tribal nations from participating in genomic research. The Center for the Ethics of Indigenous Genomic Research (CEIGR) aims to model meaningful community engagement that moves toward more inclusive and equitable research practices related to genomics. This article reflects on key successes and challenges behind CEIGR's efforts to shape Ethical, Legal and Social Implications (ELSI) research in ways that are informed by Indigenous perspectives, to locate community partnerships at the center of genomics research, and to conduct normative and empirical research with Indigenous communities that is grounded in the concepts of reciprocity, transparency and cultural competency. The structure of CEIGR represents an important shift away from a traditional model centered on a university-based principal investigators toward a partner-centered research approach that emphasizes equity and community control by distributing power and decision-making across all CEIGR partner sites. We discuss three features of CEIGR that have contributed to this shift towards an equitable, community-driven partnership: 1) balancing local priorities with collective goals; 2) distributing power in ways that promote equitable partnerships; and 3) capacity building and co-learning across partner sites. The discussion of these three areas in this article speaks to a particular strength of our Center: the interdependence among partners and collective willingness to maintain a plasticity of leadership that creates space for all of our partners to lead, support, exchange and strengthen ELSI research.

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“…The NMR to CYP2A6 genotype relationship has been well‐studied in the non‐Hispanic White population of the United States, 14 but less so in racially and ethnically diverse populations, such as ANAI people 15–18 . Thus, we sought to characterize the relationship between NMR and CYP2A6 variation in a diverse ANAI population of individuals who actively smoked.…”

Section: Introductionmentioning

confidence: 99%

Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke

Schaefer

Avey

Todd

et al. 2021

Clinical Translational Sci

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Prevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3′‐hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non‐ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype‐inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E‐08 and 4.08E‐13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9uc) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9uc. Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation.

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

Cited by 15 publications

References 41 publications

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Power Sharing, Capacity Building, and Evolving Roles in ELSI: The Center for the Ethics of Indigenous Genomic Research

Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke

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