The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population

Apinan, Roongnapa, Tassaneeyakul, Wichittra, Mahavorasirikul, Wiratchanee, Satarug, Soisangwan, Kajanawart, Sirimas, Vannaprasaht, Suda, Ruenweerayut, Ronntrai and Na-Bangchang, Kesara (2009) The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population. Environmental Toxicology and Pharmacology, 28 3: 420-424. doi:10.1016/j.etap.2009.07.004


Author Apinan, Roongnapa
Tassaneeyakul, Wichittra
Mahavorasirikul, Wiratchanee
Satarug, Soisangwan
Kajanawart, Sirimas
Vannaprasaht, Suda
Ruenweerayut, Ronntrai
Na-Bangchang, Kesara
Title The influence of CYP2A6 polymorphisms and cadmium on nicotine metabolism in Thai population
Journal name Environmental Toxicology and Pharmacology   Check publisher's open access policy
ISSN 1382-6689
1872-7077
Publication date 2009-11
Sub-type Article (original research)
DOI 10.1016/j.etap.2009.07.004
Volume 28
Issue 3
Start page 420
End page 424
Total pages 5
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Language eng
Formatted abstract
We investigated the influence of genetic, cadmium exposure and smoking status, on cytochrome P450-mediated nicotinemetabolism (CYP2A6) in 182 Thai subjects after receiving 2mg of nicotine gum chewing for 30 min. The urinary excretion of cotinine was normally distributed over a 2 h period (logarithmically transformed). Individuals with urinary cotinine levels in the ranges of 0.01–0.21, and 0.52–94.99µg/2 h were categorized as poor metabolizes (PMs: 6.5%), and extensive metabolizers (EMs: 93.5%), respectively. The majority of EMs (45%) carried homozygous wild-type genotypes (CYP2A6*1A/*1A, CYP2A6*1A/*1B and CYP2A6*1B/*1B), whereas only 1% of PMs carried these genotypes. Markedly higher frequencies of EMs were also observed in all heterozygous defective genotypes including the null genotype (*4C/*4C; 1 subject). A weak but significant positive correlation was observed between total amounts of urinary cadmium excretion and total cotinine excretion over 2 h. Our study shows generally good agreement between CYP2A6 genotypes and phenotypes. Smokers accumulated about 3–4-fold higher mean total amounts of 2-h urinary cadmium excretion (127.5±218.2 ng/2 h) than that of non-smokers (40.5±78.4 ng/2 h). Among the smokers (n = 16), homologous wild-type genotype *1/*1 was significantly the predominant genotype (6/16) compared with other defective allele including *4C/*4C. In addition, 2 h urinary excretion of cotinine in smokers of all genotypes was significantly higher than non-smokers. The proportion of smokers who smoked more than 5 cigarettes/daywas significantly higher in EMs in all CYP2A6 genotypes (n = 14) than in PMs (n = 0).
Keyword Cytochrome P450 2A6
Cadmium
Nicotine
Genetic polymorphism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Thu, 12 Nov 2009, 11:54:00 EST by Mr Andrew Martlew on behalf of National Res Centre For Environmental Toxicology