TY - JOUR
T1 - Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals
AU - Kudo, Mutsumi
AU - Saito, Yuka
AU - Sasaki, Takamitsu
AU - Akasaki, Hitomi
AU - Yamaguchi, Yuri
AU - Uehara, Moe
AU - Fujikawa, Kiyomi
AU - Ishikawa, Masaaki
AU - Hirasawa, Noriyasu
AU - Hiratsuka, Masahiro
N1 - Funding Information:
Acknowledgments: This work was supported in part by a grant from the Smoking Research Foundation and a grant from Japan Research Foundation for Clinical Pharmacology.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - GMPS
KW - HGPRT
KW - IMPDH1
KW - IMPDH2
KW - ITPA
KW - Single nucleotide polymorphism
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UR - http://www.scopus.com/inward/citedby.url?scp=73349087861&partnerID=8YFLogxK
U2 - 10.2133/dmpk.24.557
DO - 10.2133/dmpk.24.557
M3 - Article
AN - SCOPUS:73349087861
SN - 1347-4367
VL - 24
SP - 557
EP - 564
JO - Drug Metabolism and Pharmacokinetics
JF - Drug Metabolism and Pharmacokinetics
IS - 6
ER -
