C-13-caffeine breath test identifies single nucleotide polymorphisms associated with caffeine metabolism
DRUG METABOLISM AND PHARMACOKINETICS
Authors: Ishii, Michiko; Ishii, Yukimoto; Nakayama, Tomohiro; Takahashi, Yasuo; Asai, Satoshi
Abstract
We performed a caffeine (N-3-methyl-C-13) breath test (CafeBT) to determine whether it can be employed to identify caffeine metabolism-associated single nucleotide polymorphisms. The study included 130 healthy adults (mean age: 21.9 years). Saliva was collected using an Oragene (R)center dot DNA saliva collection kit. Breath samples were collected from the subjects. The subjects orally ingested 100 mg C-13-caffeine dissolved in distilled water. Subsequently, breath samples were collected in bags every 10 min for a total of 90 min. An analysis of (CO2)-C-13 in the expired breath was performed by infrared spectroscopy, and the sum of Delta(CO2)-C-13 over 90 min (S-90m) was calculated. DNA from saliva samples was genotyped using TaqMan (R) SNP Genotyping for the following genes: cytochrome P4501A2: rs762551, rs2472297, aryl-hydrocarbon receptor (rs4410790), and adenosine A(2A) receptor (rs5751876). All subjects had the genotype CC in rs2472297 alleles. No significant difference was observed in S-90m among the genotypes of rs762551 and rs5751876; however, a significant difference was found in S-90m among the genotypes of rs4410790 (C > T). Our findings suggest that the N-3 demethylation of caffeine is dependent on the rs4410790 allele and that CafeBT may be used to determine rs4410790 genotypes. (C) 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population
BEHAVIORAL AND BRAIN FUNCTIONS
Authors: Kobayashi, Hideaki; Ujike, Hiroshi; Iwata, Nakao; Inada, Toshiya; Yamada, Mitsuhiko; Sekine, Yoshimoto; Uchimura, Naohisa; Iyo, Masaomi; Ozaki, Norio; Itokawa, Masanari; Sora, Ichiro
Abstract
Background: Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors. We therefore hypothesized that variations in the A2A adenosine receptor (ADORA2A) gene modify genetic susceptibility to METH dependence/psychosis. Methods: We first analyzed variations in the exons and exon-intron boundaries of the ADORA2A gene in METH dependent/psychotic patients. Then an association analysis between these single nucleotide polymorphisms and METH dependence/psychosis was performed using a total of 171 METH dependent/psychotic patients and 229 controls. Results: We found 6 variations, of which one single nucleotide polymorphism (SNP) was novel. Significant associations were observed between the allelic and genotypic frequencies of the Exon2+751 (rs5751876) SNP and METH dependence/psychosis. These associations were observed especially in females. In the clinical feature analyses, significant associations were observed between the SNP and the patient subgroup using METH alone (i.e., without concomitant use of other substances of abuse). Conclusions: These results suggest that the ADORA2A gene could be a vulnerability factor for METH dependence/psychosis, especially in females and/or in patients using only METH.