Regular ArticleA Novel Single Nucleotide Polymorphism Altering Stability and Activity of CYP2A6☆
References (18)
- et al.
FEBS Lett.
(1998) - et al.
FEBS Lett.
(1999) - et al.
Biochem. Biophys. Res. Commun.
(1999) - et al.
Biochem. Pharmacol.
(1998) - et al.
J. Biol. Chem.
(1964) - et al.
Drug Metab. Dispos.
(1996) - et al.
J. Pharmacol. Exp. Ther.
(1997) - et al.
Nature
(1998)
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How can we Improve on Modeling Nicotine Addiction to Develop Better Smoking Cessation Treatments?
2016, International Review of NeurobiologyCitation Excerpt :Altered activity of CYP2A6 would clearly affect the bioavailability of nicotine in the systemic circulation and therefore would be a key factor involved with the addictive properties of nicotine itself. Several genetic single nucleotide polymorphisms (SNPs) have been identified that reduce function of CYP2A6*2, *4, and *5, which would lead to a prolonged effect of nicotine in the body, as well as increased gene replication of CYP2A6 in some individuals which would lead to lower sensitivity to the effects of nicotine (Ariyoshi, Sawamura, & Kamataki, 2001; Benowitz, Tyndale, Jacob, & Swan, 2002; Hadidi, Zahlsen, Idle, & Cholerton, 1997; Tyndale & Sellers, 2001). SNPs in the choline acetyltransferase (ChAT) gene (rs1880676, rs3810950, and rs868750) were also significantly associated with level of nicotine dependence (allele p-values were 0.01, 0.02, and 0.04, respectively).
CYP2A6 genetic polymorphism is associated with decreased susceptibility to squamous cell lung cancer in Japanese smokers
2015, Drug Metabolism and PharmacokineticsCitation Excerpt :Among CYP isozymes, CYP2A6 responds to the metabolism of nicotine and to the metabolic activation of a number of procarcinogens, including the tobacco-specific N-nitrosamines, N-nitrosonornicotine (NNN), and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK); this can ultimately lead to development of lung cancer [4,5]. Since the first discovery that CYP2A6 genetic polymorphism was associated with differences in the capacity of coumarin 7-hydroxylation, there have been several studies describing CYP2A6 polymorphisms and their association with tobacco-related cancer and smoking habits [6–12]. We reported previously that Japanese subjects harboring the homozygous CYP2A6*4 allele have a low risk of lung cancer [13].
Nicotine, cotinine, and β-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG
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Abbreviations used: SNP, single nucleotide polymorphism; UTR, untranslated region; PCR-SSCP, polymerase chain reaction-single strand conformation polymorphism.
- 1
To whom correspondence should be addressed at Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, Sapporo, 060-0812, Japan. Fax: +81-11-706-4978. E-mail: [email protected].