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The Significance of the Homozygous CYP2A6 Deletion on Nicotine Metabolism: A New Genotyping Method of CYP2A6 Using a Single PCR–RFLP

1999; Elsevier BV; Volume: 262; Issue: 1 Linguagem: Inglês

10.1006/bbrc.1999.1182

1090-2104

Kyoko Kitagawa, Naoki Kunugita, Takahiko Katoh, Mihi Yang, Toshihiro Kawamoto,

Nicotinic Acetylcholine Receptors Study

A convenient and specific CYP2A6 genotyping method was developed in this study. This method consisting of a single PCR–RFLP is capable of resolving the genotype into either CYP2A6*1 (wild type), CYP2A6*2, or CYP2A6*3. Among 252 Japanese persons genotyped, 241 were genotyped as the wild type, 1 as an unknown variant, and none as either CYP2A6*2 or CYP2A6*3. A homozygous deletion was found in the 10 remaining subjects. To clarify the metabolic significance of this deletion in the whole human body, urinary cotinine, the principal metabolite of nicotine, was analyzed subsequent to smoking. Cumulated urinary cotinine excretion in the homozygously CYP2A6-deleted individuals was about one-seventh compared to the control group (wild type). This study provides a firm experimental basis for correlating genotypic characterization of CYP2A6 with phenotypic expression of nicotine metabolism.