Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers

Title:Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers

Volume: 10 Issue: 4

Author(s): Norie Murayama, Makiko Shimizu, Kenta Kobayashi, Izumi Kishimoto and Hiroshi Yamazaki*

Affiliation:

• Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, 3-3165 Higashi-tamagawa Gakuen, Machida, Tokyo 194-8543,Japan

Keywords: Blood storage card, CYP2A6, plasma, saliva, urine, whole-gene deletion.

Abstract: Background: A simple method of genotyping and phenotyping cytochrome P450 2A6 (CYP2A6) was previously reported using individual blood samples and urinary caffeine metabolite ratios of 1,7-dimethyluric acid (17U) to 1-methylxanthine (1X).

Objective: Blood spotted onto storage cards and salivary caffeine metabolites were analyzed in 27 healthy non-smoking Japanese volunteers with no prior abstention from dietary caffeine intake.

Methods: 1,7-Dimethylxanthine (17X), 17U, 1X, and caffeine levels in spot saliva samples were determined in Japanese non-smokers by high-performance liquid chromatography under normal dietary caffeine consumption.

Results: 17U/17X ratios in saliva were almost constant over time, but those of 17U/1X were variable in two subjects tested before and 1-2.5 h after caffeine treatment (a cup of black tea). In seven subjects, 17U/17X ratios in saliva were highly correlated with those in plasma (r = 0.98, p < 0.01) and well correlated with those in urine samples (r = 0.78, p < 0.05). The average 17U/17X ratios, but not 17U/1X ratios, in saliva under dietary caffeine consumption obtained from subjects with CYP2A6*1/*4 (n=11) and CYP2A6*4/*4 (whole-gene deletion, n=2) genotypes were significantly lower than those from subjects with wild-type CYP2A6*1/*1 (n=14). Genotyping was done by a multiplex real-time polymerase chain reaction method using blood spotted onto storage cards.

Conclusion: The present results suggest that the decreased CYP2A6 function associated with the whole-gene deletion genotype (determined using blood samples) could be detected using 17U/17X ratios, but not 17U/1X ratios, in spot saliva samples under normal dietary caffeine consumption in Japanese non-smokers, just as it could be detected using urinary 17U/1X ratios.

Cite this article as:

Murayama Norie, Shimizu Makiko, Kobayashi Kenta, Kishimoto Izumi and Yamazaki Hiroshi*, Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers, Drug Metabolism Letters 2016; 10 (4) . https://dx.doi.org/10.2174/1872312810666161114144008

DOI https://dx.doi.org/10.2174/1872312810666161114144008	Print ISSN 1872-3128
Publisher Name Bentham Science Publisher	Online ISSN 1874-0758