Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals

Mutsumi Kudo, Yuka Saito, Takamitsu Sasaki, Hitomi Akasaki, Yuri Yamaguchi, Moe Uehara, Kiyomi Fujikawa, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)557-564
Number of pages8
JournalDrug Metabolism and Pharmacokinetics
Issue number6
Publication statusPublished - 2009


  • GMPS
  • IMPDH1
  • IMPDH2
  • ITPA
  • Single nucleotide polymorphism


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