<i>CYP2A6</i>
            Genotyping Methods and Strategies Using Real-Time and End Point PCR Platforms

Wassenaar, Catherine A.; Zhou, Qian; Tyndale, Rachel F.

doi:10.2217/pgs.15.156

Cited by 21 publications

(35 citation statements)

References 53 publications

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“…Genotyping was performed using a two-step allele-specific polymerase chain reaction approach, or an allele-specific TaqMan single nucleotide polymorphism genotyping assay (Applied Biosystems) and real-time polymerase chain reaction, as described previously [42]. The CYP2A6 alleles *2 , *4 , *7 , *9 , *12 , *17 , and *35 have been associated with a decrease or loss of CYP2A6 enzyme activity and rates of nicotine metabolism [18, 43, 44], whereas the *1B allele associates with faster nicotine metabolism [45].…”

Section: Methodsmentioning

confidence: 99%

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer

Tanner

Henderson

Buchwald

et al. 2017

Pharmacogenetics and Genomics

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Objectives The Northern Plains (NP) and Southwest (SW) American Indian populations differ in their smoking patterns and lung cancer incidence. We aimed to compare CYP2A6 genetic variation and CYP2A6 enzyme activity (representative of the rate of nicotine metabolism) between the two tribal populations, as these have previously been associated with differences in smoking, quitting, and lung cancer risk. Methods American Indians (N=636) were recruited from two different tribal populations (NP in South Dakota, SW in Arizona) as part of a study conducted as part of the Collaborative to Improve Native Cancer Outcomes P50 project. A questionnaire assessed smoking-related traits and demographics. Participants were genotyped for CYP2A6 genetic variants *1B, *2, *4, *7, *9, *12, *17, and *35. Plasma and/or saliva samples were used to measure nicotine’s metabolites cotinine and 3′-hydroxycotinine and determine CYP2A6 activity (3′-hydroxcotinine/cotinine, i.e. the nicotine metabolite ratio, NMR). Results The overall frequency of genetically reduced nicotine metabolizers, those with CYP2A6 decrease- or loss-of-function alleles, was lower in the NP compared to the SW (P=0.0006). CYP2A6 genotype was associated with NMR in both tribal groups (NP P<0.001, SW P=0.04). Notably, the rate of nicotine metabolism was higher in NP compared to SW smokers (P=0.03), and in comparison to other ethnic groups in the United States. Of the variables studied, CYP2A6 genotype was the only variable to significantly independently influence NMR among smokers in both tribal populations (NP P<0.001, SW P=0.05). Conclusions Unique CYP2A6 allelic patterns and rates of nicotine metabolism among these American Indian populations suggest different risks for smoking and tobacco-related disease.

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Section: Methodsmentioning

confidence: 99%

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer

Tanner

Henderson

Buchwald

et al. 2017

Pharmacogenetics and Genomics

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“…Participants were genotyped for CYP2A6 reduced/null activity alleles predominantly found in African populations, CYP2A6*17 , *20 , *23-*28 , *31 , *35 , and for those also found in other racial populations, CYP2A6*2 , *4 , *9 and *12 [15, 23–27]. No participants with *12, *20, *23, or *28 alleles were identified.…”

Section: Methodsmentioning

confidence: 99%

Disposition kinetics and metabolism of nicotine and cotinine in African American smokers

Benowitz

Helen

Dempsey

et al. 2016

Pharmacogenetics and Genomics

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Objective The rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk. The prevalence of CYP2A6 gene variants differs by race, with greater numbers in African American (AA) compared to Caucasians. We studied nicotine disposition kinetics and metabolism by CYP2A6 genotype and enzymatic activity, as measured by nicotine metabolite ratio (NMR), in AA smokers. Methods Subjects were administered IV infusions of deuterium-labeled nicotine and cotinine. Plasma and urine concentrations of nicotine and metabolites were measured, and pharmacokinetic parameters estimated. Results Pharmacokinetic parameters and urine metabolite excretion data were analyzed by CYP2A6 genotype and by NMR. A number of gene variants were associated with markedly reduced nicotine and cotinine clearances. NMR was strongly correlated with nicotine (r=0.72) and cotinine (r=0.80) clearances. Subjects with higher NMR excreted significantly greater nicotine C-oxidation and lower non C-oxidation products compared to lower NMR subjects. Conclusions CYP2A6 genotype, NMR and nicotine pharmacokinetic data may inform studies of individual differences in smoking behavior and biomarkers of nicotine exposure.

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“…In addition, all samples (n = 472) were prepared for genotyping using nested real-time PCR and Taqman copy number assay methods. 30,31…”

Section: Sample Processing and Storagementioning

confidence: 99%

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

Claw

Beans

Lee

et al. 2019

Nicotine &Amp; Tobacco Research

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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.

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CYP2A6 Genotyping Methods and Strategies Using Real-Time and End Point PCR Platforms

Cited by 21 publications

References 53 publications

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer

Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer

Disposition kinetics and metabolism of nicotine and cotinine in African American smokers

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

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