13C-caffeine breath test identifies single nucleotide polymorphisms associated with caffeine metabolism

• Published in: Drug metabolism and pharmacokinetics 2020-06, Vol.35 (3), p.321-328
• Main Authors: Ishii, Michiko, Ishii, Yukimoto, Nakayama, Tomohiro, Takahashi, Yasuo, Asai, Satoshi
• Format: Article
• Language: English
• Subjects: 13C-caffeine breath test; Adenosine A2A receptor; Aryl hydrocarbon receptor; CYP1A2; Single nucleotide polymorphism
• ISSN: 1347-4367; 1880-0920
• DOI: 10.1016/j.dmpk.2020.03.003

We performed a caffeine (N-3-methyl-13C) 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®•DNA saliva collection kit. Breath samples were collected from the subjects. The subjects orally ingested 100 mg 13C-caffeine dissolved in distilled water. Subsequently, breath samples were collected in bags every 10 min for a total of 90 min. An analysis of 13CO2 in the expired breath was performed by infrared spectroscopy, and the sum of Δ13CO2 over 90 min (S90m) was calculated. DNA from saliva samples was genotyped using TaqMan® SNP Genotyping for the following genes: cytochrome P4501A2: rs762551, rs2472297, aryl-hydrocarbon receptor (rs4410790), and adenosine A2A receptor (rs5751876). All subjects had the genotype CC in rs2472297 alleles. No significant difference was observed in S90m among the genotypes of rs762551 and rs5751876; however, a significant difference was found in S90m 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. [Display omitted]