@article {Nunoya437, author = {Ken-Ichi Nunoya and Tsuyoshi Yokoi and Kanzo Kimura and Tadashi Kainuma and Kunio Satoh and Moritoshi Kinoshita and Tetsuya Kamataki}, title = {A New CYP2A6 Gene Deletion Responsible for the In Vivo Polymorphic Metabolism of (+)-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one Hydrochloride in Humans }, volume = {289}, number = {1}, pages = {437--442}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {(+)-Cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) is a newly developed drug as a platelet-activating factor receptor antagonist. The disposition of SM-12502 was investigated in plasma from 28 healthy Japanese volunteers after a single i.v. administration of SM-12502. Three of 28 subjects were phenotyped as poor metabolizers (PMs). Genomic DNAs from three extensive metabolizers or three PMs of SM-12502 were analyzed by Southern blot analysis with CYP2A6 cDNA as a probe. DNAs from three PMs digested with SacI and SphI showed novel restriction fragment length polymorphisms (RFLPs); one type without 4.5- and 2.6-kb fragments and a weak density of a 6.4-kb fragment (E-type), and the other type without 7.1- and 5.5-kb restriction fragments (C'-type) as compared with three extensive metabolizers, respectively. The deletional restriction fragments specific to three PMs in SacI- and SphI-RFLPs were identified as CYP2A6. Using polymerase chain reaction-RFLP analyses of the gene from the three PMs, we found that the exon 1, exon 8, and exon 9 in CYP2A6 were absent. A new RFLP characterized by SacI and SphI was found to be due to the entire gene deletion of the three exons and was associated with the decreased metabolism of SM-12502. This study demonstrates a new deletional allele in the human CYP2A6gene responsible for the poor metabolic phenotype of SM-12502. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/289/1/437}, eprint = {https://jpet.aspetjournals.org/content/289/1/437.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }