Genetic Variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS Genes in Japanese Individuals

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 24; no. 6; pp. 557 - 564
• Main Authors: Kudo, Mutsumi, Saito, Yuka, Sasaki, Takamitsu, Akasaki, Hitomi, Yamaguchi, Yuri, Uehara, Moe, Fujikawa, Kiyomi, Ishikawa, Masaaki, Hirasawa, Noriyasu, Hiratsuka, Masahiro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2009; Japanese Society for the Study of Xenobiotics
• Subjects: Asian People - genetics; Azathioprine - pharmacology; Carbon-Nitrogen Ligases; Exons; Gene Frequency; Genes, Recessive; Genetic Variation; Genotype; GMPS; Guanosine Monophosphate - metabolism; HGPRT; Humans; Hypoxanthine Phosphoribosyltransferase - genetics; IMPDH1; IMPDH2; Inflammatory Bowel Diseases - genetics; Inosine Triphosphatase; Introns; ITPA; Mercaptopurine - pharmacology; Methyltransferases - genetics; Molecular Sequence Data; Mutation; Myeloid-Lymphoid Leukemia Protein - genetics; Oncogene Proteins, Fusion - genetics; Pharmacogenetics; Phenotype; Polymorphism, Single Nucleotide; Pyrophosphatases - genetics; single nucleotide polymorphism; Thionucleotides - metabolism; GMPS; HGPRT; IMPDH1; single nucleotide polymorphism; IMPDH2; ITPA
• ISSN: 1347-4367; 1880-0920; 1880-0920
• DOI: 10.2133/dmpk.24.557

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.