Document Detail


Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals.
MedLine Citation:
PMID:  20045992     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Mutsumi Kudo; Yuka Saito; Takamitsu Sasaki; Hitomi Akasaki; Yuri Yamaguchi; Moe Uehara; Kiyomi Fujikawa; Masaaki Ishikawa; Noriyasu Hirasawa; Masahiro Hiratsuka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  24     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2009  
Date Detail:
Created Date:  2010-01-04     Completed Date:  2010-04-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  557-64     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, Sendai, Miyagi 980-8578, Japan.
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MeSH Terms
Descriptor/Qualifier:
5'-Guanylic Acid / metabolism
6-Mercaptopurine / pharmacology
Asian Continental Ancestry Group / genetics*
Azathioprine / pharmacology
Carbon-Nitrogen Ligases
Exons
Gene Frequency*
Genes, Recessive
Genetic Variation*
Genotype
Humans
Hypoxanthine Phosphoribosyltransferase / genetics*
Inflammatory Bowel Diseases / genetics*
Introns
Methyltransferases / genetics
Molecular Sequence Data
Mutation
Myeloid-Lymphoid Leukemia Protein / genetics*
Oncogene Proteins, Fusion / genetics*
Pharmacogenetics
Phenotype
Polymorphism, Single Nucleotide
Pyrophosphatases / genetics
Thionucleotides / metabolism
Chemical
Reg. No./Substance:
0/MLL-GMPS fusion protein, human; 0/Oncogene Proteins, Fusion; 0/Thionucleotides; 149025-06-9/Myeloid-Lymphoid Leukemia Protein; 446-86-6/Azathioprine; 50-44-2/6-Mercaptopurine; 76310-16-2/guanosine 5'-monophosphorothioate; 85-32-5/5'-Guanylic Acid; EC 2.1.1.-/Methyltransferases; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase; EC 3.6.1.-/Pyrophosphatases; EC 3.6.1.-/inosine triphosphatase; EC 6.3.-/Carbon-Nitrogen Ligases; EC 6.3.4.1/GMP synthase

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