CYP2A6

Summary

Gene Symbol: CYP2A6
Description: cytochrome P450 family 2 subfamily A member 6
Alias: CPA6, CYP2A, CYP2A3, CYPIIA6, P450C2A, P450PB, cytochrome P450 2A6, 1,4-cineole 2-exo-monooxygenase, coumarin 7-hydroxylase, cytochrome P450 IIA3, cytochrome P450(I), cytochrome P450, family 2, subfamily A, polypeptide 6, cytochrome P450, subfamily IIA (phenobarbital-inducible), polypeptide 6, flavoprotein-linked monooxygenase, xenobiotic monooxygenase
Species: human
Products:     CYP2A6

Top Publications

  1. Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R, et al. Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther. 2006;80:282-97 pubmed
    ..However, there are few data on the ethnic influences of the CYP2A6-nicotine metabolism relationship, particularly with regard to black subjects...
  2. Kwon J, Nakajima M, Chai S, Yom Y, Kim H, Yamazaki H, et al. Nicotine metabolism and CYP2A6 allele frequencies in Koreans. Pharmacogenetics. 2001;11:317-23 pubmed
    b>CYP2A6 is a major catalyst of nicotine metabolism to cotinine. Previously, we demonstrated that the interindividual difference in nicotine metabolism is related to a genetic polymorphism of the CYP2A6 gene in Japanese...
  3. Fujieda M, Yamazaki H, Saito T, Kiyotani K, Gyamfi M, Sakurai M, et al. Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. Carcinogenesis. 2004;25:2451-8 pubmed
    We reported previously that subjects homozygous for the cytochrome P450 2A6 (CYP2A6) (*)4 have a lower risk of lung cancer...
  4. Schoedel K, Hoffmann E, Rao Y, Sellers E, Tyndale R. Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics. 2004;14:615-26 pubmed
    Genetically variable CYP2A6 is the primary enzyme that inactivates nicotine to cotinine...
  5. Liu T, David S, Tyndale R, Wang H, Zhou Q, Ding P, et al. Associations of CYP2A6 genotype with smoking behaviors in southern China. Addiction. 2011;106:985-94 pubmed publisher
    ..about socio-demographic status and smoking behaviors and informative alleles were genotyped for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6*4,*5,*7,*9 and *10). The frequencies of CYP2A6*4, *5, *7, *9 and *10 alleles were 8...
  6. Miles J, Bickmore W, Brook J, McLaren A, Meehan R, Wolf C. Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. Nucleic Acids Res. 1989;17:2907-17 pubmed
    ..The P450IIA (CYP2A) gene subfamily was found to be closely linked to the P450IIB (CYP2B) subfamily and their chromosomal location ..
  7. Oscarson M, McLellan R, Gullsten H, Agundez J, Benitez J, Rautio A, et al. Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett. 1999;460:321-7 pubmed
    The polymorphic human cytochrome P450 2A6 (CYP2A6) metabolises a number of drugs, activates a variety of precarcinogens and constitutes the major nicotine C-oxidase...
  8. Tan W, Chen G, Xing D, Song C, Kadlubar F, Lin D. Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer. 2001;95:96-101 pubmed
    b>Cytochrome P450 2A6 (CYP2A6) plays an important role in the oxidation of nicotine and in the activation of tobacco-related carcinogens, such as N-nitrosodimethylamine, N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-..
  9. Kiyotani K, Yamazaki H, Fujieda M, Iwano S, Matsumura K, Satarug S, et al. Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9). Pharmacogenetics. 2003;13:689-95 pubmed
    One of seven poor metabolizers of coumarin found in Thai subjects was previously genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9...

More Information

Publications118 found, 100 shown here

  1. Johnstone E, Benowitz N, Cargill A, Jacob R, Hinks L, Day I, et al. Determinants of the rate of nicotine metabolism and effects on smoking behavior. Clin Pharmacol Ther. 2006;80:319-30 pubmed
    ..However, known alleles of CYP2A6 associated with fast or slow metabolism are relatively uncommon, and there remains considerable variation in ..
  2. Peamkrasatam S, Sriwatanakul K, Kiyotani K, Fujieda M, Yamazaki H, Kamataki T, et al. In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais. Drug Metab Pharmacokinet. 2006;21:475-84 pubmed
    The association between the distribution characteristics of CYP2A6 catalytic activities toward nicotine and coumarin, and the frequency distribution of CYP2A6 variant alleles reported was estimated in 120 healthy Thais...
  3. Kaida Y, Inui N, Suda T, Nakamura H, Watanabe H, Chida K. The CYP2A6*4 allele is determinant of S-1 pharmacokinetics in Japanese patients with non-small-cell lung cancer. Clin Pharmacol Ther. 2008;83:589-94 pubmed publisher
    ..be converted enzymatically to 5-FU to exert its antitumor effect, and this conversion is principally catalyzed by CYP2A6. Forty-six non-small-cell lung cancer patients were enrolled...
  4. Fujita K, Yamamoto W, Endo S, Endo H, Nagashima F, Ichikawa W, et al. CYP2A6 and the plasma level of 5-chloro-2, 4-dihydroxypyridine are determinants of the pharmacokinetic variability of tegafur and 5-fluorouracil, respectively, in Japanese patients with cancer given S-1. Cancer Sci. 2008;99:1049-54 pubmed publisher
    ..CDHP is added to prevent degradation of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase. CYP2A6 is involved in the biotransformation of FT to 5-FU...
  5. Kong S, Lim H, Nam B, Kook M, Kim Y, Ryu K, et al. Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes in metastatic gastric cancer. Pharmacogenomics. 2009;10:1147-55 pubmed publisher
    S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5-fluorouracil mainly by CYP2A6. We evaluated the association between CYP2A6 polymorphisms and treatment outcome in metastatic gastric cancer patients treated with S-1 ..
  6. Loriot M, Rebuissou S, Oscarson M, Cenee S, Miyamoto M, Ariyoshi N, et al. Genetic polymorphisms of cytochrome P450 2A6 in a case-control study on lung cancer in a French population. Pharmacogenetics. 2001;11:39-44 pubmed
    b>Cytochrome P450 2A6 (CYP2A6) is involved in the C-oxidation of nicotine and in the metabolic activation of tobacco nitrosamines...
  7. Tyndale R, Sellers E. Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. Ther Drug Monit. 2002;24:163-71 pubmed
    ..The genetically polymorphic CYP2A6 enzyme is responsible for the majority of the metabolic inactivation of nicotine to cotinine (12-14)...
  8. Ariyoshi N, Sekine H, Saito K, Kamataki T. Characterization of a genotype previously designated as CYP2A6 D-type: CYP2A6*4B, another entire gene deletion allele of the CYP2A6 gene in Japanese. Pharmacogenetics. 2002;12:501-4 pubmed
    b>CYP2A6 is known as an enzyme responsible for the metabolism of several clincally used drugs such as tegafur...
  9. Ariyoshi N, Miyamoto M, Umetsu Y, Kunitoh H, Dosaka Akita H, Sawamura Y, et al. Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers. Cancer Epidemiol Biomarkers Prev. 2002;11:890-4 pubmed
    b>Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine...
  10. Oscarson M, McLellan R, Asp V, Ledesma M, Bernal Ruiz M, Sinues B, et al. Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. Hum Mutat. 2002;20:275-83 pubmed
    The human CYP2A6 enzyme metabolizes certain drugs and pre-carcinogens and appears to be the most important enzyme for nicotine metabolism...
  11. Haberl M, Anwald B, Klein K, Weil R, Fuss C, Gepdiremen A, et al. Three haplotypes associated with CYP2A6 phenotypes in Caucasians. Pharmacogenet Genomics. 2005;15:609-24 pubmed
    The human cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several xenobiotic compounds of clinical or toxicological importance. We aimed to identify genetic variants and major CYP2A6 haplotypes associated with CYP2A6 phenotypic variation...
  12. Kamataki T, Fujieda M, Kiyotani K, Iwano S, Kunitoh H. Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk. Biochem Biophys Res Commun. 2005;338:306-10 pubmed
    Analyzing the CYP2A6 gene of subjects who showed a poor metabolic phenotype toward SM-12502, we discovered a novel mutant allele (CYP2A6*4C) lacking the whole CYP2A6 gene...
  13. Anderson G, Chan L. Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Clin Pharmacokinet. 2016;55:1353-1368 pubmed
    ..Nicotine is a substrate of CYP2A6, which is induced by oestrogen, resulting in lower concentrations of nicotine in females than in males, especially ..
  14. Rysz M, Bromek E, Haduch A, Sadakierska Chudy A, Daniel W. Damage to the Brain Serotonergic System Increases the Expression of Liver Cytochrome P450. Drug Metab Dispos. 2015;43:1345-52 pubmed publisher
    ..Simultaneously, the activity and protein level of liver CYP1A, CYP3A1, and CYP2C11 rose (the activity of CYP2A/2B/2C6/2D was not significantly changed)...
  15. Dinger J, Meyer M, Maurer H. Development of an in vitro cytochrome P450 cocktail inhibition assay for assessing the inhibition risk of drugs of abuse. Toxicol Lett. 2014;230:28-35 pubmed publisher
    ..in pooled human liver microsomes: phenacetin (alpha-naphthoflavone for CYP1A2), coumarin (tranylcypromine, CYP2A6), bupropion (sertraline, CYP2B6), amodiaquine (trimethoprim, CYP2C8), diclofenac (sulfaphenazole, CYP2C9), ..
  16. Florek E, Kulza M, Piekoszewski W, Gomółka E, Jawień W, Teżyk A, et al. Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats. Pharmacol Rep. 2015;67:921-7 pubmed publisher
    ..Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use ..
  17. Ho M, Ring N, Amaral K, Doshi U, Li A. Human Enterocytes as an In Vitro Model for the Evaluation of Intestinal Drug Metabolism: Characterization of Drug-Metabolizing Enzyme Activities of Cryopreserved Human Enterocytes from Twenty-Four Donors. Drug Metab Dispos. 2017;45:686-691 pubmed publisher
    ..female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), ..
  18. Gunawan A, Jakaria -, Listyarini K, Furqon A, Sumantri C, Akter S, et al. Transcriptome signature of liver tissue with divergent mutton odour and flavour using RNA deep sequencing. Gene. 2018;676:86-94 pubmed publisher
    ..Among the DEGs, metabolic phase I related genes belonging to the cytochrome P450 CYP2A6 were dominantly expressed...
  19. Dovrtělová G, Zendulka O, Nosková K, Jurica J, Pes O, Dušek J, et al. Effect of Endocannabinoid Oleamide on Rat and Human Liver Cytochrome P450 Enzymes in In Vitro and In Vivo Models. Drug Metab Dispos. 2018;46:913-923 pubmed publisher
    ..The activities of CYP2C6, CYP2A, and CYP3A and the levels of hormones were not altered...
  20. Chen X, Owoseni E, Salamat J, Cederbaum A, Lu Y. Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5. Arch Biochem Biophys. 2018;657:65-73 pubmed publisher
    Tobacco and alcohol are often co-abused. Nicotine can enhance alcoholic fatty liver, and CYP2A6 (CYP2A5 in mice), a major metabolism enzyme for nicotine, can be induced by alcohol...
  21. Mohajeri M, Behnam B, Cicero A, Sahebkar A. Protective effects of curcumin against aflatoxicosis: A comprehensive review. J Cell Physiol. 2017;: pubmed publisher
    ..aroused from its structure, modulation of the immune system as reflected by interleukin-1? and transforming growth factor-?, and interfering with AF's biotransformation by cytochrome P450 isoenzymes CYP1A, CYP3A, CYP2A, CYP2B, and CYP2C.
  22. Gupta R, van Dongen J, Fu Y, Abdellaoui A, Tyndale R, Velagapudi V, et al. Epigenome-wide association study of serum cotinine in current smokers reveals novel genetically driven loci. Clin Epigenetics. 2019;11:1 pubmed publisher
    ..As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine ..
  23. Tomankova V, Liskova B, Skalova L, Bártíková H, Bousova I, Jourova L, et al. Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity. Life Sci. 2015;133:15-20 pubmed publisher
    ..Higher activity of CYP2A5 (CYP2A6 human ortholog) could lead to altered metabolism of drug substrates of this enzyme (valproic acid, nicotine, ..
  24. Deeni Y, Ibbotson S, Woods J, Wolf C, Smith G. Cytochrome P450 CYP1B1 interacts with 8-methoxypsoralen (8-MOP) and influences psoralen-ultraviolet A (PUVA) sensitivity. PLoS ONE. 2013;8:e75494 pubmed publisher
    ..We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism...
  25. Zhang B, Madden P, Gu J, Xing X, Sankar S, Flynn J, et al. Uncovering the transcriptomic and epigenomic landscape of nicotinic receptor genes in non-neuronal tissues. BMC Genomics. 2017;18:439 pubmed publisher
    ..CHRNA4 transcription was highly correlated with genes involved in the nicotine metabolism, including CYP2A6, UGT2B7, and FMO3...
  26. Untereiner A, Pavlidou A, Druzhyna N, Papapetropoulos A, Hellmich M, Szabo C. Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells. Biochem Pharmacol. 2018;149:174-185 pubmed publisher
    ..There was a significant increase in the expression of the drug-metabolizing cytochrome P450 enzymes CYP1A2 and CYP2A6 in 5-FU-resistant cells...
  27. Zhang N, Qi M, Zhao L, Zhu M, Guo J, Liu J, et al. Curcumin Prevents Aflatoxin B? Hepatoxicity by Inhibition of Cytochrome P450 Isozymes in Chick Liver. Toxins (Basel). 2016;8: pubmed
    ..the mRNA and/or activity of enzymes responsible for the bioactivation of AFB? into AFBO-including CYP1A1, CYP1A2, CYP2A6, and CYP3A4-were significantly induced in liver microsomes after 2-week exposure to AFB?...
  28. Murphy S, Sipe C, Choi K, Raddatz L, Koopmeiners J, Donny E, et al. Low Cotinine Glucuronidation Results in Higher Serum and Saliva Cotinine in African American Compared to White Smokers. Cancer Epidemiol Biomarkers Prev. 2017;26:1093-1099 pubmed publisher
    ..Cotinine is metabolized by UGT2B10 and CYP2A6, and low UGT2B10 activity is common in AA, due to the prevalence of a UGT2B10 splice variant...
  29. Liju V, Jeena K, Kuttan R. Chemopreventive activity of turmeric essential oil and possible mechanisms of action. Asian Pac J Cancer Prev. 2014;15:6575-80 pubmed
    ..Moreover TEO significantly (P<0.001) inhibited isoforms of cytochrome p450 (CYP1A1, CYP1A2, CYP2B1/2, CYP2A, CYP2B and CYP3A) enzymes in vitro, which are involved in the activation of carcinogens...
  30. Ross K, Gubner N, Tyndale R, Hawk L, Lerman C, George T, et al. Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking. Pharmacol Biochem Behav. 2016;148:1-7 pubmed publisher
    ..nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity...
  31. Dhoro M, Zvada S, Ngara B, Nhachi C, Kadzirange G, Chonzi P, et al. CYP2B6*6, CYP2B6*18, Body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe. BMC Pharmacol Toxicol. 2015;16:4 pubmed publisher
    ..EFV plasma concentrations were measured by HPLC and genomic DNA genotyped for variants in the CYP2B6, CYP2A6 and ABCB1 genes...
  32. Yoshida R, Nakajima M, Nishimura K, Tokudome S, Kwon J, Yokoi T. Effects of polymorphism in promoter region of human CYP2A6 gene (CYP2A6*9) on expression level of messenger ribonucleic acid and enzymatic activity in vivo and in vitro. Clin Pharmacol Ther. 2003;74:69-76 pubmed
    ..There are genetic polymorphisms in the human CYP2A6 gene...
  33. Higashi E, Fukami T, Itoh M, Kyo S, Inoue M, Yokoi T, et al. Human CYP2A6 is induced by estrogen via estrogen receptor. Drug Metab Dispos. 2007;35:1935-41 pubmed
    Human CYP2A6, which is predominantly expressed in liver, is a key enzyme responsible for the metabolism of nicotine, coumarin, and some pharmaceutical drugs...
  34. Emamghoreishi M, Bokaee H, Keshavarz M, Ghaderi A, Tyndale R. CYP2A6 allele frequencies in an Iranian population. Arch Iran Med. 2008;11:613-7 pubmed
    Genetic polymorphism of CYP2A6 gene is a major causal factor in the large interindividual differences in nicotine metabolism. It may have an impact on smoking behavior and smoke-related cancer susceptibility...
  35. Pearce R, Cohen Wolkowiez M, Sampson M, Kearns G. The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013;41:1686-94 pubmed publisher
    ..3A4, 3A5, and 3A7 catalyzed metronidazole 2-hydroxylation at rates substantially greater than control vector, and CYP2A6 catalyzed 2-hydroxymetronidazole formation at rates 6-fold higher than the next most active enzyme...
  36. Ariyoshi N, Sekine H, Nakayama K, Saito K, Miyamoto A, Kamataki T. Identification of deletion-junction site of CYP2A6*4B allele lacking entire coding region of CYP2A6 in Japanese. Pharmacogenetics. 2004;14:701-5 pubmed
  37. Veiga M, Asimus S, Ferreira P, Martins J, Cavaco I, Ribeiro V, et al. Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam. Eur J Clin Pharmacol. 2009;65:355-63 pubmed publisher
    ..The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 ..
  38. Imaizumi T, Higaki Y, Hara M, Sakamoto T, Horita M, Mizuta T, et al. Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population. Carcinogenesis. 2009;30:1729-34 pubmed publisher
    ..controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking...
  39. Tamaki Y, Arai T, Sugimura H, Sasaki T, Honda M, Muroi Y, et al. Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan. Drug Metab Pharmacokinet. 2011;26:516-22 pubmed
    ..investigate the relationship between lung cancer cases in Japan and variant alleles of cytochrome P450 (CYP) 2A6 (CYP2A6*4), CYP2A13 (CYP2A13*1-*10), CYP4B1 (CYP4B1*1-*7), sulfotransferase 1A1 (SULT1A1*2), glutathione S-transferase M1 (..
  40. Chenoweth M, Schnoll R, Novalen M, Hawk L, George T, Cinciripini P, et al. The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio. Nicotine Tob Res. 2016;18:491-5 pubmed publisher
    ..Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism...
  41. Borrego Soto G, Costilla Esquivel A, Padilla Rivas G, Cázares Samaniego P, Posadas Valay R, Velasco Castañón J, et al. [Association between genotype and allele frequencies of CYP2A6*12 and rs16969968 in CHRNA5 variants with smoking and body mass index in young subjects from Northeast Mexico]. Rev Med Chil. 2015;143:1377-85 pubmed publisher
    Several studies have reported that variants rs16969968 G>A of the CHRNA5 gene and CYP2A6*12 of the CYP2A6 gene are associated with smoking and smoking refusal, respectively...
  42. Matsuda Y, Saoo K, Yamakawa K, Yokohira M, Suzuki S, Kuno T, et al. Overexpression of CYP2A6 in human colorectal tumors. Cancer Sci. 2007;98:1582-5 pubmed
    b>CYP2A6 metabolizes various nitrosamines, such as those in the diet and in tobacco smoke, which have been implicated as risk factors for colorectal tumors...
  43. Ueng Y, Chen C, Chung Y, Liu T, Chang Y, Lo W, et al. Mechanism-based inhibition of cytochrome P450 (CYP)2A6 by chalepensin in recombinant systems, in human liver microsomes and in mice in vivo. Br J Pharmacol. 2011;163:1250-62 pubmed publisher
    ..was studied in vitro using human liver microsomes and bacterial membranes expressing genetic variants of human CYP2A6. Effects in vivo were studied in C57BL/6J mice...
  44. Bloom A, Harari O, Martinez M, Zhang X, McDonald S, Murphy S, et al. A compensatory effect upon splicing results in normal function of the CYP2A6*14 allele. Pharmacogenet Genomics. 2013;23:107-16 pubmed publisher
    A synonymous variant in the first exon of CYP2A6, rs1137115 (51G>A), defines the common reference allele CYP2A6*1A, and is associated with lower mRNA expression and slower in-vivo nicotine metabolism...
  45. Burkhardt T, Letzel T, Drewes J, Grassmann J. Comprehensive assessment of Cytochrome P450 reactions: A multiplex approach using real-time ESI-MS. Biochim Biophys Acta. 2015;1850:2573-81 pubmed publisher
    ..Multiplex experiments using the highly specific CYP2A6 with its corresponding substrate coumarin as well as the highly promiscuous CYP3A4 with testosterone were ..
  46. Bořek Dohalská L, Valášková P, Kubickova B, Sulc M, Křesinová Z, Cajthaml T, et al. A study on 17alpha-ethinylestradiol metabolism in rat and Pleurotus ostreatus. Neuro Endocrinol Lett. 2015;36 Suppl 1:5-12 pubmed
    ..hydroxylated by several rat CYPs, among them CYP2C6 and 2C11 are most efficient in 2-hydroxy-EE2 formation, while CYP2A and 3A catalyze EE2 hydroxylation to the second product...
  47. Hryhorowicz S, Walczak M, Zakerska Banaszak O, Słomski R, Skrzypczak Zielinska M. Pharmacogenetics of Cannabinoids. Eur J Drug Metab Pharmacokinet. 2018;43:1-12 pubmed publisher
    ..ABCG2, SLC6A, biotransformation, biosynthesis, and bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14...
  48. Burian M, Freudenstein J, Tegtmeier M, Naser Hijazi B, Henneicke von Zepelin H, Legrum W. Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin. Int J Clin Pharmacol Ther. 2003;41:141-7 pubmed
    ..Coumarin, used in the treatment of chronic venous diseases, is mainly metabolized to non-toxic 7-hydroxy-coumarin by CYP2A6. At least, 3 variant alleles, CYP2A6*2, CYP2A6*3 and CYP2A6*4A, have been shown to encode catalytically defective ..
  49. Gambier N, Batt A, Marie B, Pfister M, Siest G, Visvikis Siest S. Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort. Pharmacogenomics J. 2005;5:271-5 pubmed
    This study was designed in order to investigate the influence of the genetic polymorphism of CYP2A6 on the amount of smoking...
  50. Mwenifumbo J, Al Koudsi N, Ho M, Zhou Q, Hoffmann E, Sellers E, et al. Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Hum Mutat. 2008;29:679-88 pubmed publisher
    b>Cytochrome P450 2A6 (CYP2A6) is a human enzyme best known for metabolizing tobacco-related compounds, such as nicotine, cotinine (COT), and nitrosamine procarcinogens...
  51. Xie C, Wen X, Ding P, Liu T, He Y, Niu Z, et al. Influence of CYP2A6*4 genotypes on maternal serum cotinine among Chinese nonsmoking pregnant women. Nicotine Tob Res. 2014;16:406-12 pubmed publisher
    ..This study investigated the influence of CYP2A6*4 genotypes on serum cotinine among nonsmoking pregnant women...
  52. Dubroff J, Doot R, Falcone M, Schnoll R, Ray R, Tyndale R, et al. Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. J Nucl Med. 2015;56:1724-9 pubmed publisher
    The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in ..
  53. Štěpánková M, Krasulová K, Doricakova A, Kurka O, Anzenbacher P, Dvorak Z. Optical isomers of dihydropyridine calcium channel blockers display enantiospecific effects on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450. Toxicol Lett. 2016;262:173-186 pubmed publisher
    ..All CCBs induced CYP2A6, CYP2B6 and CYP3A4 mRNA and protein in human hepatocytes, and there were not differences between the enantiomers...
  54. Kanemoto K, Fukuta K, Kawai N, Tozawa K, Ochiai M, Okamoto K, et al. Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype. PLoS ONE. 2016;11:e0167374 pubmed publisher
    ..the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13...
  55. Tanner J, Zhu A, Claw K, Prasad B, Korchina V, Hu J, et al. Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism. Pharmacogenet Genomics. 2018;28:7-16 pubmed publisher
    ..e. cytochrome P450 2A6 (CYP2A6), enzyme activity]...
  56. Djordjevic N, Carrillo J, Gervasini G, Jankovic S, Aklillu E. In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population. Eur J Clin Pharmacol. 2010;66:571-8 pubmed publisher
    The main aim of the study was to investigate the distribution of cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the Serbian population...
  57. Da Silva F, da Silva J, Allgayer M, Simon C, Dias J, Dos Santos C, et al. Genotoxic biomonitoring of tobacco farmers: Biomarkers of exposure, of early biological effects and of susceptibility. J Hazard Mater. 2012;225-226:81-90 pubmed publisher
    ..In order to verify the relationship between genetic susceptibility and biomarkers GSTT1, GSTM1, GSTP1, CYP2A6, PON, OGG1, RAD51, XRCC1, and XRCC4 genes polymorphism were evaluated...
  58. Fasinu P, Gutmann H, Schiller H, James A, Bouic P, Rosenkranz B. The potential of Sutherlandia frutescens for herb-drug interaction. Drug Metab Dispos. 2013;41:488-97 pubmed publisher
    ..S. frutescens showed inhibitory potency for CYP1A2 (IC(50) = 41.0 µg/ml), CYP2A6 (IC(50) = 160 µg/ml), CYP2B6 (IC(50) = 20.0 µg/ml), CYP2C8 (IC(50) = 22.4 µg/ml), CYP2C9 (IC(50) = 23...
  59. Bloom A, Hartz S, Baker T, Chen L, Piper M, Fox L, et al. Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide. Ann Am Thorac Soc. 2014;11:1003-10 pubmed publisher
  60. Benowitz N, St Helen G, Dempsey D, Jacob P, Tyndale R. Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity. Pharmacogenet Genomics. 2016;26:340-50 pubmed publisher
    The rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk...
  61. Wang K, Chen X, Ward S, Liu Y, Ouedraogo Y, Xu C, et al. CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model. Int J Obes (Lond). 2019;43:475-486 pubmed publisher
    b>CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver. Hepatic CYP2A6 expression is increased in patients with non-alcoholic fatty liver disease (NAFLD). In mice, hepatic CYP2A5 is induced by high fat diet (HFD) feeding...
  62. Kim D, Wu Z, Guengerich F. Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. J Biol Chem. 2005;280:40319-27 pubmed
    ..The attenuation is caused in part to lower binding affinity for NADPH-P450 reductase, but the K476E mutant did not achieve the wild-type coumarin 7-hydroxylation activity even at high reductase concentrations. ..
  63. Cho M, Castaldi P, Wan E, Siedlinski M, Hersh C, DeMeo D, et al. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. Hum Mol Genet. 2012;21:947-57 pubmed publisher
    ..08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.
  64. Sarkar J, Kumar A. Thermo-responsive polymer aided spheroid culture in cryogel based platform for high throughput drug screening. Analyst. 2016;141:2553-67 pubmed publisher
    ..18 ng per day per 10(4) cells), CYP1A1 (304.92 pg per min per 10(4) cells), CYP2A6 (441.23 nM per min per 10(4) cells) and phase II metabolic activity (386...
  65. Tanner J, Prasad B, Claw K, Stapleton P, Chaudhry A, Schuetz E, et al. Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors. J Pharmacol Exp Ther. 2017;360:129-139 pubmed
    b>Cytochrome P450 2A6 CYP2A6: metabolizes several clinically relevant substrates, including nicotine, the primary psychoactive component in cigarette smoke...
  66. Yuan J, Nelson H, Carmella S, Wang R, Kuriger Laber J, Jin A, et al. CYP2A6 genetic polymorphisms and biomarkers of tobacco smoke constituents in relation to risk of lung cancer in the Singapore Chinese Health Study. Carcinogenesis. 2017;38:411-418 pubmed publisher
    b>Cytochrome P450 2A6 (CYP2A6) catalyzes the metabolism of nicotine and the tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)...
  67. Yang L, Zou S, Shu C, Song Y, Sun Y, Zhang W, et al. CYP2A6 Polymorphisms Associate with Outcomes of S-1 Plus Oxaliplatin Chemotherapy in Chinese Gastric Cancer Patients. Genomics Proteomics Bioinformatics. 2017;15:255-262 pubmed publisher
    ..treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 (CYP2A6) and outcomes of S-1 plus oxaliplatin (SOX) chemotherapy treatment...
  68. Jeong J, Park S, Ahn Y, Ryu M, Ryoo B, Kong S, et al. Associations between CYP2A6 polymorphisms and outcomes of adjuvant S-1 chemotherapy in patients with curatively resected gastric cancer. Gastric Cancer. 2017;20:146-155 pubmed publisher
    Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6)...
  69. Stresser D, Perloff E, Mason A, Blanchard A, Dehal S, Creegan T, et al. Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole. Drug Metab Dispos. 2016;44:1424-30 pubmed publisher
    ..In a reversible inhibition assay of the major drug-metabolizing cytochrome P450 (P450) isoforms, CYP2A6 and CYP2E1 exhibited IC50 values of 24 µM and 42 µM, respectively with all other isoforms exhibiting values &..
  70. Kumar S, Sinha N, Gerth K, Rahman M, Yallapu M, Midde N. Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications. Biochem Biophys Res Commun. 2017;491:675-680 pubmed publisher
    ..Of the seven CYP enzymes tested, the mRNA of CYP1B1, CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes...
  71. Taghavi T, Arger C, Heil S, Higgins S, Tyndale R. Longitudinal Influence of Pregnancy on Nicotine Metabolic Pathways. J Pharmacol Exp Ther. 2018;364:238-245 pubmed publisher
    ..N-glucuronidation, and the pregnancy-induced influences on the activity of enzymes mediating these pathways (CYP2A6 and UGT2B10, respectively)...
  72. Jeong S, Nguyen P, Desta Z. Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A. Antimicrob Agents Chemother. 2009;53:541-51 pubmed publisher
    ..CYP2C9, CYP2C19, and CYP3A (half-maximal [50%] inhibitory concentrations, <6 microM); its effect on CYP1A2, CYP2A6, CYP2C8, and CYP2D6 was marginal (<25% inhibition at 100 microM voriconazole)...
  73. Yun C, Shimada T, Guengerich F. Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol. 1991;40:679-85 pubmed
    ..These results emphasize the need to characterize individual P-450 enzymes in order to understand their functions in the context of more complex systems. ..
  74. Zhang X, Amemo K, Ameno S, Iwahashi K, Kinoshita H, Kubota T, et al. Lack of association between smoking and CYP2A6 gene polymorphisms in A Japanese population. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2001;36:486-90 pubmed
    This study determined the genotypes of the CYP2A6 gene in 96 smokers and 141 non-smokers in a Japanese population. The frequencies of wild-type of the CYP2A6* 1 and those with a whole deletion of the CYP2A6 gene were 93 (96.9%) and 3 (3...
  75. Tsukino H, Kuroda Y, Qiu D, Nakao H, Imai H, Katoh T. Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma. Int J Cancer. 2002;100:425-8 pubmed
    ..The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies...
  76. Dalekos G, Obermayer Straub P, Bartels M, Maeda T, Kayser A, Braun S, et al. Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis C virus infection. J Hepatol. 2003;39:800-6 pubmed
    Cytochromes P4502A6 (CYP2A6) and P4501A2 (CYP1A2) were described as hepatic autoantigens in the autoimmune polyglandular syndrome type-1 (APS-1)...
  77. Lalovic B, Phillips B, Risler L, Howald W, Shen D. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004;32:447-54 pubmed
  78. Kiyotani K, Fujieda M, Yamazaki H, Shimada T, Guengerich F, Parkinson A, et al. Twenty one novel single nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians. Drug Metab Pharmacokinet. 2002;17:482-7 pubmed
    We sequenced all nine exons and exon-intron junctions of the CYP2A6 gene from 33 Japanese and 28 Caucasians...
  79. Gemignani F, Landi S, Szeszenia Dabrowska N, Zaridze D, Lissowska J, Rudnai P, et al. Development of lung cancer before the age of 50: the role of xenobiotic metabolizing genes. Carcinogenesis. 2007;28:1287-93 pubmed
    ..Heterozygote carriers of SNPs in CYP1A2 1545T>C, -164C>A and -740T>G; CYP2A6 -47A>C; MDR1 3435T>C; NAT1 1088T>A and 1095A>C; GSTA2 S112T; GSTM3 V224I and MTHFR A222V had altered ..
  80. Caceres D, Alvarado S, Martinez P, Quiñones L. [Relation of genetic variants of CYP2A6 with tobacco dependence and smoking habit in Chilean subjects. A pilot study]. Rev Med Chil. 2012;140:436-41 pubmed publisher
    ..To assess the prevalence of allelic and genotype variants of CYP2A6 in a sample of Chilean subjects and to evaluate their relationship with smoking and tobacco dependence...
  81. Pan L, Yang X, Li S, Jia C. Association of CYP2A6 gene polymorphisms with cigarette consumption: a meta-analysis. Drug Alcohol Depend. 2015;149:268-71 pubmed publisher
    A meta-analysis was performed to assess the association of hepatic cytochrome P450 2A6 (CYP2A6) gene polymorphisms with cigarette consumption...
  82. Ito T, Tsuji M, Mori Y, Kanda H, Hidaka T, Kakamu T, et al. EFFECT OF CYP2A6*4 GENETIC POLYMORPHISMS ON SMOKING BEHAVIORS AND NICOTINE DEPENDENCE IN A GENERAL POPULATION OF JAPANESE MEN. Fukushima J Med Sci. 2015;61:125-30 pubmed publisher
    Nicotine in cigarettes is metabolized primarily by CYP2A6-catalyzed oxidation. The CYP2A6*4 allele, in which CYP2A6 is a homozygous whole-deletion variant, completely lacks enzyme activity...
  83. Phillips I, Shephard E, Ashworth A, Rabin B. Isolation and sequence of a human cytochrome P-450 cDNA clone. Proc Natl Acad Sci U S A. 1985;82:983-7 pubmed
    ..Analysis by Southern blotting indicated that the human cytochrome P-450 encoded by pHP450(1) is part of a multigene family. ..
  84. Hoffman S, Fernandez Salguero P, Gonzalez F, Mohrenweiser H. Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19. J Mol Evol. 1995;41:894-900 pubmed
    Cytochrome P450 genes from the CYP2A, CYP2B, and CYP2F subfamilies form a tight cluster which we have localized on the detailed physical map of human chromosome 19...
  85. Kitagawa K, Kunugita N, Kitagawa M, Kawamoto T. CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem. 2001;276:17830-5 pubmed
    ..technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP), a novel polymorphism of CYP2A6, CYP2A6*6, was detected in 0.4% of the Japanese population. To study the enzymatic properties of the CYP2A6...
  86. Arab Alameddine M, Di Iulio J, Buclin T, Rotger M, Lubomirov R, Cavassini M, et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Clin Pharmacol Ther. 2009;85:485-94 pubmed publisher
    ..Plasma samples from 169 human immunodeficiency virus (HIV) patients characterized for CYP2B6, CYP2A6, and CYP3A4/5 allelic diversity were used to build up a population pharmacokinetic model using NONMEM (non-linear ..
  87. Liu H, Hu Y, Liu Y, He Y, Li W, Yang L. Hydroxylation of tanshinone IIa in human liver microsomes is specifically catalysed by cytochrome P4502A6. Xenobiotica. 2009;39:382-90 pubmed publisher
    ..inhibitor, cDNA-expressed human cytochrome P450s, correlation assay, and kinetics study demonstrated that CYP2A6 was the specific isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 microM) in human liver ..
  88. Rodriguez S, Cook D, Gaunt T, Nightingale C, Whincup P, Day I. Combined analysis of CHRNA5, CHRNA3 and CYP2A6 in relation to adolescent smoking behaviour. J Psychopharmacol. 2011;25:915-23 pubmed publisher
    b>CYP2A6 influences smoking uptake in adolescence. Genetic variation in the CHRNA5-CHRNA3 region influences smoking behaviour in adults. However, their combined effects on smoking in adolescence have not been tested to date...
  89. Da Silva F, da Silva J, Nunes E, Benedetti D, Kahl V, Rohr P, et al. Application of the buccal micronucleus cytome assay and analysis of PON1Gln192Arg and CYP2A6*9(-48T>G) polymorphisms in tobacco farmers. Environ Mol Mutagen. 2012;53:525-34 pubmed publisher
    ..Polymorphisms in PONIGln192Arg and CYP2A6*9(-48T>G) were evaluated to verify the relationship between genetic susceptibility and the measured biomarkers...
  90. López Flores L, Pérez Rubio G, Ramirez Venegas A, Ambrocio Ortiz E, Sansores R, Falfan Valencia R. Data on polymorphisms in CYP2A6 associated to risk and predispose to smoking related variables. Data Brief. 2017;15:86-91 pubmed publisher
    ..contains data on the single nucleotide polymorphisms (SNPs) rs1137115, rs1801272 and rs28399433 rs4105144 in CYP2A6 associated to smoking related variables in Mexican Mestizo smokers (Pérez-Rubio et al., 2017) [1]...
  91. Bart A, Scott E. Structural and functional effects of cytochrome b5 interactions with human cytochrome P450 enzymes. J Biol Chem. 2017;292:20818-20833 pubmed publisher
    ..NMR results revealed that P450 enzymes bound to either b5 α4-5 (CYP2A6 and CYP2E1) or this region and α2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for b..
  92. Ding S, Lake B, Friedberg T, Wolf C. Expression and alternative splicing of the cytochrome P-450 CYP2A7. Biochem J. 1995;306 ( Pt 1):161-6 pubmed
    ..These clones were CYP2A6, CYP2A7 and an alternatively spliced version of CYP2A7 (CYP2A7AS)...