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

Abstract 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...

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Autores principales:	Krista R. Schaefer, Jaedon P. Avey, Michael R. Todd, Julie A. Beans, Denise A. Dillard, Laura M. Shireman, Timothy A. Thornton, Rachel F. Tyndale, Kenneth E. Thummel, Renee F. Robinson, Katrina G. Claw
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/6b432934769e459884438c5771c4f6b3
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spelling	oai:doaj.org-article:6b432934769e459884438c5771c4f6b32021-11-19T17:51:35ZNicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke1752-80621752-805410.1111/cts.13115https://doaj.org/article/6b432934769e459884438c5771c4f6b32021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13115https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract 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 CYP2A61B 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.Krista R. SchaeferJaedon P. AveyMichael R. ToddJulie A. BeansDenise A. DillardLaura M. ShiremanTimothy A. ThorntonRachel F. TyndaleKenneth E. ThummelRenee F. RobinsonKatrina G. ClawWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2474-2486 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Krista R. Schaefer Jaedon P. Avey Michael R. Todd Julie A. Beans Denise A. Dillard Laura M. Shireman Timothy A. Thornton Rachel F. Tyndale Kenneth E. Thummel Renee F. Robinson Katrina G. Claw Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
description	Abstract 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 CYP2A61B 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.
format	article
author	Krista R. Schaefer Jaedon P. Avey Michael R. Todd Julie A. Beans Denise A. Dillard Laura M. Shireman Timothy A. Thornton Rachel F. Tyndale Kenneth E. Thummel Renee F. Robinson Katrina G. Claw
author_facet	Krista R. Schaefer Jaedon P. Avey Michael R. Todd Julie A. Beans Denise A. Dillard Laura M. Shireman Timothy A. Thornton Rachel F. Tyndale Kenneth E. Thummel Renee F. Robinson Katrina G. Claw
author_sort	Krista R. Schaefer
title	Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
title_short	Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
title_full	Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
title_fullStr	Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
title_full_unstemmed	Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
title_sort	nicotine metabolism and its association with cyp2a6 genotype among indigenous people in alaska who smoke
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/6b432934769e459884438c5771c4f6b3
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Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke

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