Polymorphisms of CYP2A6 and its practical consequences.

Article Details

Citation

Raunio H, Rautio A, Gullsten H, Pelkonen O

Polymorphisms of CYP2A6 and its practical consequences.

Br J Clin Pharmacol. 2001 Oct;52(4):357-63.

PubMed ID
11678779 [ View in PubMed
]
Abstract

CYP2A6 is an hepatic enzyme predominantly with some expression in specialized extrahepatic cell types. The CYP2A6 enzyme has a somewhat restricted active site, accepting only a few xenobiotics as substrates. Interest in CYP2A6 has risen considerably after nicotine and some tobacco specific nitrosamines were established as high-affinity substrates for this enzyme. Recently, the organization and structures of the CYP2A gene cluster and several polymorphic alleles of the CYP2A6 gene have been characterized. Two alleles with a point mutation and at least three different types of gene deletion, all leading to deficient gene function, have been found. The frequencies of these alleles vary considerably among different ethnic populations, the deletion alleles being most common in Orientals (up to 20%). The frequency of point mutations are low in all populations studied thus far (< 3%). Several case-control studies have addressed the relationship between CYP2A6 status and smoking habits as well as the role of CYP2A6 polymorphism in lung cancer risk. Studies in Japanese suggest that CYP2A6 poor metabolizer genotypes result in altered nicotine kinetics and may lower cigarette smoking elicited lung cancer risk, whereas similar studies in Caucasian populations have not revealed any clear associations between variant CYP2A6 genotypes and smoking behaviour or lung cancer predisposition.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
OmalizumabHigh affinity immunoglobulin epsilon receptor subunit betaProteinHumans
Yes
Inhibitor
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
HalothaneCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
LetrozoleCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Inhibitor
Details
MethoxsalenCytochrome P450 2A6ProteinHumans
Unknown
Inhibitor
Details
NicotineCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Inhibitor
Details
Valproic acidCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
Drug Interactions
DrugsInteraction
Acetaminophen
Letrozole
The metabolism of Acetaminophen can be decreased when combined with Letrozole.
Acetaminophen
Seratrodast
The metabolism of Acetaminophen can be decreased when combined with Seratrodast.
Acetaminophen
Hydrocortisone
The metabolism of Acetaminophen can be increased when combined with Hydrocortisone.
Acetaminophen
Eletriptan
The metabolism of Acetaminophen can be increased when combined with Eletriptan.
Acetaminophen
Prednisolone phosphate
The metabolism of Acetaminophen can be increased when combined with Prednisolone phosphate.