Annotated PGx Gene Information for CYP2A6
Submitted by: Manki Ho, Jill Mwenifumbo, Ryan Owen (PharmGKB), Rachel Tyndale PNAT
Reviewed by: Under Review
Submitted date: Feb 28, 2007
| Gene HGNC Name: | CYP2A6 |
|---|---|
| Gene Common Name |
CYP2A6 |
| Introductory Information: | CYP2A6 genetic variation and substrates CYP2A6 is a highly polymorphic gene. Currently, there are 23 numbered (e.g. CYP2A6*2) CYP2A6 alleles (http://www.imm.ki.se/CYPalleles). The CYP2A6 enzyme is involved in the metabolism of several pharmaceutical agents. It is the major metabolic enzyme involved in coumarin 7-hydroxylation. Coumarin is a selective substrate of CYP2A6 and is a good probe drug [PMID: 2334398]. The S-oxidation of the platelet activating factor antagonist SM-12502 is primarily mediated by CYP2A6 and variations in CYP2A6 genotype are responsible for the poor metabolic phenotype of SM-12502 [PMID: 10087035]. CYP2A6 also plays major role in converting the antineoplastic pro-drug Tegafur to 5-fluorouracil and genetic variations have been linked to altered therapeutic responses [PMID: 12042667]. CYP2A6 also activates a number of pro-carcinogens such as the tobacco specific nitrosoamines NNK, NNAL and NNN [PMID: 1902334]. Perhaps the most notable of the therapeutics metabolized by CYP2A6 is nicotine. In vivo approximately 80% of absorbed nicotine is inactivated to cotinine via C-oxidation and in vitro CYP2A6 mediates 90% of this reaction [PMID: 8937855 and 9316878]. CYP2A6 smoking and cancer Nicotine is the primary compound in tobacco that establishes and maintains tobacco dependence [PMID: 4009494]. Genetic variation in CYP2A6 influences the pharmacokinetics of nicotine and subsequently smoking behaviours. CYP2A6 decreased or loss-of-function variants have been associated with an altered risk of becoming nicotine dependent, a decreased risk of being a current smoker, a decrease in cigarette consumption and an increased likelihood of cessation. However, these finding have not been uniformly confirmed [PMID: 15735609]. Genetic variation in CYP2A6 has also been associated with altered risk for a variety of cancers in some but not all, studies [PMID: 16176798]. |
| Key PubMed IDs: | PMIDs: 2334398, 10087035, 12042667, 1902334, 8937855, 9316878, 4009494, 15735609, 16176798 |
| Key Pathways: | Nicotine pathway |
| Drugs/Substrates (with PMID) |
Coumarin, SM-12502, Tegafur, nicotine, 5-fluorouracil |
| Important Variants: | Important Variant Information for CYP2A6 : 58 bp gene conversion, C45906A, A45948G, C47441T, 50364-50365 del TT, A50707T, A52553G |
| Important Haplotypes: |
Important Haplotype Information for CYP2A6 : CYP2A6*1B, CYP2A6*1x2, CYP2A6*2, CYP2A6*4, CYP2A6*7, CYP2A6*9, CYP2A6*10, CYP2A6*12, CYP2A6*17, CYP2A6*20 |