Linked Life Data

11393269

Source:http://linkedlifedata.com/resource/pubmed/id/11393269

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-6-6
pubmed:abstractText
Cytochrome P450 2A6 is an important human hepatic P450 which activates precarcinogens and oxidizes some drug constituents such as coumarin, halothane, and the major nicotine C-oxidase. Genetic polymorphism exists in the CYP2A6 gene. CYP2A6*1 (wild type) is responsible for the 7-hydroxylation of coumarin. The point mutation (T to A) in codon 160 leads to a single amino acid substitution (Leu to His) and the resulting protein, CYP2A*2 is unable to 7-hydroxylate coumarin. Gene conversion in exons 3, 6, and 8 between the CYP2A6 and the CYP2A7 genes creates another variant, CYP2A6*3. In this study, healthy male and female Turkish volunteers (n = 50) were administered 2 mg coumarin, and urine samples were analyzed for their content of the coumarin metabolite, 7-hydroxycoumarin (7OHC), by high-performance liquid chromatography (HPLC). Genetic polymorphism for CYP2A6 was detected by using two-step polymerase chain reaction (PCR) to identify CYP2A6*1, CYP2A6*2, and CYP2A6*3 in 13 of these subjects. The percentage of the dose excreted of total 7OHC in relation to CYP2A6 genotype and excretion of nicotine/cotinine was also evaluated to demonstrate the role of CYP2A6 in nicotine metabolism. The majority of Turkish subjects (68%) excreted less than 60% of the 2-mg dose as coumarin metabolite. The allelic frequencies were detected as 0.88 for CYP2A6*1 allele; 0.12 for CYP2A6*3 allele in 13 individuals. No heterozygous and homozygous individuals were identified for the CYP2A6*2 allelic variant. Phenotyping and genotyping for drug metabolizing enzymes are of great importance in studies correlating precarcinogen activation or drug metabolism to the CYP2A6 genotype in smoking behavior when populations are investigated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0960-3271
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
179-84
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11393269-Adult, pubmed-meshheading:11393269-Aged, pubmed-meshheading:11393269-Amino Acid Substitution, pubmed-meshheading:11393269-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:11393269-Cotinine, pubmed-meshheading:11393269-Coumarins, pubmed-meshheading:11393269-Cytochrome P-450 Enzyme System, pubmed-meshheading:11393269-Female, pubmed-meshheading:11393269-Gene Frequency, pubmed-meshheading:11393269-Genotype, pubmed-meshheading:11393269-Humans, pubmed-meshheading:11393269-Isoenzymes, pubmed-meshheading:11393269-Male, pubmed-meshheading:11393269-Middle Aged, pubmed-meshheading:11393269-Mixed Function Oxygenases, pubmed-meshheading:11393269-Nicotine, pubmed-meshheading:11393269-Phenotype, pubmed-meshheading:11393269-Point Mutation, pubmed-meshheading:11393269-Polymorphism, Genetic, pubmed-meshheading:11393269-Smoking, pubmed-meshheading:11393269-Turkey, pubmed-meshheading:11393269-Umbelliferones
pubmed:year
2001
pubmed:articleTitle
Determination of coumarin metabolism in Turkish population.
pubmed:affiliation
Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey.
pubmed:publicationType
Journal Article, Comparative Study