title: Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals.
abstract: Thiopurines (such as azathioprine and 6-mercaptopurine) are widely used for the treatment of patients suffering from malignancies, rheumatic disease, inflammatory bowel disease and solid organ transplant rejection. These drugs are activated and eliminated by a number of enzymes in the human body. This analyzes all the exons and exon-intron junctions of 5 enzyme genes (hypoxanthine-guanine phosphoribosyltransferase, HGPRT; inosine triphosphate pyrophosphatase, ITPA; inosine monophosphate dehydrogenases 1 and 2, IMPDH1 and IMPDH2 and guanosine monophosphate synthetase, GMPS) involved in the metabolism of thiopurine drugs. Twelve novel single nucleotide polymorphisms (SNPs) (HGPRT: IVS6-12C>A (frequency:0.003); ITPA: 569T>C (Phe189Phe, 0.003); IMPDH1: IVS8-15C>A (0.003), IVS9+227A>G (0.003), IVS17+115C>T (0.003), and 930C>T (Thr310Thr, 0.005); IMPDH2: IVS1+50G>T (0.003), IVS2+15G>A (0.010), IVS3-20G>A (0.003), 609C>T (Arg203Arg, 0.003), and 1534C>T (Arg512Trp, 0.003); and GMPS: 1563T>C (Gly521Gly, 0.003)) and 7 known SNPs (ITPA: 94C>A (Pro32Thr, 0.005), 138G>A (Gln46Gln, 0.586), and 563G>A (Glu187Glu, 0.433); IMPDH1: 987G>C (Leu329Leu, 0.113) and 1575A>G (Ala525Ala, 0.620) and GMPS: IVS5-7T>C (0.153), 993A>G (Thr331Thr, 0.153)) were identified in 200 Japanese subjects. These data should provide useful information for thiopurine therapy in the Japanese and as well as other Asian populations.
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kudo
authors.forename: Yuka
authors.initials: Y
authors.lastname: Saito
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Akasaki
authors.forename: Yuri
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Moe
authors.initials: M
authors.lastname: Uehara
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D044466:Asian People / Q000235:genetics*; D001379:Azathioprine / Q000494:pharmacology; D019731:Carbon-Nitrogen Ligases; D005091:Exons; D005787:Gene Frequency; D005808:Genes, Recessive; D014644:Genetic Variation; D005838:Genotype; D006157:Guanosine Monophosphate / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007438:Introns; D015122:Mercaptopurine / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics; D013873:Thionucleotides / Q000378:metabolism; D000097630:Inosine Triphosphatase
chemical_list: D001379:Azathioprine; D019731:Carbon-Nitrogen Ligases; D006157:Guanosine Monophosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D015122:Mercaptopurine; D008780:Methyltransferases; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D011755:Pyrophosphatases; D013873:Thionucleotides; D000097630:Inosine Triphosphatase; C418134:MLL-GMPS fusion protein, human; C066524:guanosine 5'-monophosphorothioate; C020828:GMP synthase (glutamine-hydrolyzing)