CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people
ObjectivesAlaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, ha...
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2012
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ftcdlib:oai:escholarship.org:ark:/13030/qt10g3w1c6 2023-10-25T01:44:35+02:00 CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people Binnington, Matthew J Zhu, Andy ZX Renner, Caroline C Lanier, Anne P Hatsukami, Dorothy K Benowitz, Neal L Tyndale, Rachel F 429 - 440 2012-06-01 https://escholarship.org/uc/item/10g3w1c6 unknown eScholarship, University of California qt10g3w1c6 https://escholarship.org/uc/item/10g3w1c6 CC-BY-NC-SA Pharmacogenetics and Genomics, vol 22, iss 6 Biological Sciences Biomedical and Clinical Sciences Genetics Tobacco Smoke and Health American Indian or Alaska Native Tobacco Brain Disorders Good Health and Well Being Adult Aged Alaska Aryl Hydrocarbon Hydroxylases Cotinine Cytochrome P-450 CYP2A6 Cytochrome P-450 CYP2B6 Epistasis Genetic Female Gene Frequency Genetic Association Studies Genetic Variation Population Genotype Humans Male Middle Aged Models Nicotine Oxidoreductases N-Demethylating Population Groups Smoking Alaska Native people CYP2A6 CYP2B6 Pharmacology and Pharmaceutical Sciences Pharmacology & Pharmacy article 2012 ftcdlib 2023-09-25T18:04:11Z ObjectivesAlaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward the increased risk.MethodsAN people (n=400) residing in the Bristol Bay region of South Western Alaska were recruited for a cross-sectional study on tobacco use. They were genotyped for CYP2A6*1X2A, *1X2B, *1B, *2, *4, *7, *8, *9, *10, *12, *17, *35 and CYP2B6*4, *6, *9 and provided plasma and urine samples for the measurement of nicotine and metabolites.ResultsCYP2A6 and CYP2B6 variant frequencies among the AN Yupik people (n=361) were significantly different from those in other ethnicities. Nicotine metabolism [as measured by the plasma and urinary ratio of metabolites trans-3'-hydroxycotinine to cotinine (3HC/COT)] was significantly associated with CYP2A6 (P<0.001), but not CYP2B6 genotype (P=0.95) when controlling for known covariates. It was noteworthy that the plasma 3HC/COT ratios were high in the entire Yupik people, and among the Yupik CYP2A6 wild-type participants, they were substantially higher than those in previously characterized racial/ethnic groups (P<0.001 vs. Caucasians and African Americans).ConclusionYupik AN people have a unique CYP2A6 genetic profile that associated strongly with in-vivo nicotine metabolism. More rapid CYP2A6-mediated nicotine and nitrosamine metabolism in the Yupik people may modulate the risk of tobacco-related diseases. Article in Journal/Newspaper Yupik Alaska University of California: eScholarship Indian |
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University of California: eScholarship |
op_collection_id |
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language |
unknown |
topic |
Biological Sciences Biomedical and Clinical Sciences Genetics Tobacco Smoke and Health American Indian or Alaska Native Tobacco Brain Disorders Good Health and Well Being Adult Aged Alaska Aryl Hydrocarbon Hydroxylases Cotinine Cytochrome P-450 CYP2A6 Cytochrome P-450 CYP2B6 Epistasis Genetic Female Gene Frequency Genetic Association Studies Genetic Variation Population Genotype Humans Male Middle Aged Models Nicotine Oxidoreductases N-Demethylating Population Groups Smoking Alaska Native people CYP2A6 CYP2B6 Pharmacology and Pharmaceutical Sciences Pharmacology & Pharmacy |
spellingShingle |
Biological Sciences Biomedical and Clinical Sciences Genetics Tobacco Smoke and Health American Indian or Alaska Native Tobacco Brain Disorders Good Health and Well Being Adult Aged Alaska Aryl Hydrocarbon Hydroxylases Cotinine Cytochrome P-450 CYP2A6 Cytochrome P-450 CYP2B6 Epistasis Genetic Female Gene Frequency Genetic Association Studies Genetic Variation Population Genotype Humans Male Middle Aged Models Nicotine Oxidoreductases N-Demethylating Population Groups Smoking Alaska Native people CYP2A6 CYP2B6 Pharmacology and Pharmaceutical Sciences Pharmacology & Pharmacy Binnington, Matthew J Zhu, Andy ZX Renner, Caroline C Lanier, Anne P Hatsukami, Dorothy K Benowitz, Neal L Tyndale, Rachel F CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
topic_facet |
Biological Sciences Biomedical and Clinical Sciences Genetics Tobacco Smoke and Health American Indian or Alaska Native Tobacco Brain Disorders Good Health and Well Being Adult Aged Alaska Aryl Hydrocarbon Hydroxylases Cotinine Cytochrome P-450 CYP2A6 Cytochrome P-450 CYP2B6 Epistasis Genetic Female Gene Frequency Genetic Association Studies Genetic Variation Population Genotype Humans Male Middle Aged Models Nicotine Oxidoreductases N-Demethylating Population Groups Smoking Alaska Native people CYP2A6 CYP2B6 Pharmacology and Pharmaceutical Sciences Pharmacology & Pharmacy |
description |
ObjectivesAlaska Native (AN) people have a high prevalence of tobacco use and associated morbidity and mortality when compared with the general USA population. Variations in the CYP2A6 and CYP2B6 genes, encoding enzymes responsible for nicotine metabolic inactivation and procarcinogen activation, have not been characterized in AN and may contribute toward the increased risk.MethodsAN people (n=400) residing in the Bristol Bay region of South Western Alaska were recruited for a cross-sectional study on tobacco use. They were genotyped for CYP2A6*1X2A, *1X2B, *1B, *2, *4, *7, *8, *9, *10, *12, *17, *35 and CYP2B6*4, *6, *9 and provided plasma and urine samples for the measurement of nicotine and metabolites.ResultsCYP2A6 and CYP2B6 variant frequencies among the AN Yupik people (n=361) were significantly different from those in other ethnicities. Nicotine metabolism [as measured by the plasma and urinary ratio of metabolites trans-3'-hydroxycotinine to cotinine (3HC/COT)] was significantly associated with CYP2A6 (P<0.001), but not CYP2B6 genotype (P=0.95) when controlling for known covariates. It was noteworthy that the plasma 3HC/COT ratios were high in the entire Yupik people, and among the Yupik CYP2A6 wild-type participants, they were substantially higher than those in previously characterized racial/ethnic groups (P<0.001 vs. Caucasians and African Americans).ConclusionYupik AN people have a unique CYP2A6 genetic profile that associated strongly with in-vivo nicotine metabolism. More rapid CYP2A6-mediated nicotine and nitrosamine metabolism in the Yupik people may modulate the risk of tobacco-related diseases. |
format |
Article in Journal/Newspaper |
author |
Binnington, Matthew J Zhu, Andy ZX Renner, Caroline C Lanier, Anne P Hatsukami, Dorothy K Benowitz, Neal L Tyndale, Rachel F |
author_facet |
Binnington, Matthew J Zhu, Andy ZX Renner, Caroline C Lanier, Anne P Hatsukami, Dorothy K Benowitz, Neal L Tyndale, Rachel F |
author_sort |
Binnington, Matthew J |
title |
CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
title_short |
CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
title_full |
CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
title_fullStr |
CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
title_full_unstemmed |
CYP2A6 and CYP2B6 genetic variation and its association with nicotine metabolism in South Western Alaska Native people |
title_sort |
cyp2a6 and cyp2b6 genetic variation and its association with nicotine metabolism in south western alaska native people |
publisher |
eScholarship, University of California |
publishDate |
2012 |
url |
https://escholarship.org/uc/item/10g3w1c6 |
op_coverage |
429 - 440 |
geographic |
Indian |
geographic_facet |
Indian |
genre |
Yupik Alaska |
genre_facet |
Yupik Alaska |
op_source |
Pharmacogenetics and Genomics, vol 22, iss 6 |
op_relation |
qt10g3w1c6 https://escholarship.org/uc/item/10g3w1c6 |
op_rights |
CC-BY-NC-SA |
_version_ |
1780742264207704064 |