Pharmacogenetic significance of inosine triphosphatase

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Bibliography

• 1  Duley JA, Florin TH: Thiopurine therapies: problems, complexities, and progress with monitoring thioguanine nucleotides. Ther. Drug Monit.27,647–654 (2005).• Critical review of the present state of knowledge of mercaptopurine metabolism.
  Medline CASGoogle Scholar
• 2  Poppe D, Tiede I, Fritz G et al.: Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. J. Immunol.176,640–651 (2006).
  Medline CASGoogle Scholar
• 3  Tiede I, Fritz G, Strand S et al.: CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest.111,1133–1145 (2003).
  Medline CASGoogle Scholar
• 4  Marinaki AM, Ansari A, Duley JA et al.: Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics14,181–187 (2004).•• Establishes the possible correlation between inosine triphosphatase (ITPase) deficiency and azathioprine-induced adverse drug reations.
  Medline CASGoogle Scholar
• 5  Marinaki AM, Duley JA, Arenas M et al.: Mutation in the ITPA gene predicts intolerance to azathioprine. Nucleosides Nucleotides Nucleic Acids23,1393–1397 (2004).
  Medline CASGoogle Scholar
• 6  Sumi S, Marinaki AM, Arenas M et al.: Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum. Genet.111,360–367 (2002).
  Google Scholar
• 7  Weber J, Senior AE: Bi-site catalysis in F1-ATPase: does it exist? J. Biol. Chem.276,35422–35428 (2001).
  Medline CASGoogle Scholar
• 8  Myrnes B, Guddal PH, Krokan H: Metabolism of dITP in HeLa cell extracts, incorporation into DNA by isolated nuclei and release of hypoxanthine from DNA by a hypoxanthine-DNA glycosylase activity. Nucleic Acids Res.10,3693–3701 (1982).
  Medline CASGoogle Scholar
• 9  Spee JH, de Vos WM, Kuipers OP: Efficient random mutagenesis method with adjustable mutation frequency by use of PCR and dITP. Nucleic Acids Res.21,777–778 (1993).
  Medline CASGoogle Scholar
• 10  Vanderheiden BS: Genetic studies of human erythrocyte inosine triphosphatase. Biochem. Genet.3,289–297 (1969).
  Medline CASGoogle Scholar
• 11  Holmes SL, Turner BM, Hirschhorn K: Human inosine triphosphatase: catalytic properties and population studies. Clin. Chim. Acta97,143–153 (1979).
  Medline CASGoogle Scholar
• 12  Vanderheiden BS: Human erythrocyte ‘ITPase’: an ITP pyrophosphohydrolase. Biochim. Biophys. Acta215,555–558 (1970).
  Medline CASGoogle Scholar
• 13  Cao H, Hegele RA: DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. J. Hum. Genet.47,620–622 (2002).
  Medline CASGoogle Scholar
• 14  Stenmark P, Kursula P, Flodin S et al.: Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T. J. Biol. Chem.282,3182–3187 (2007).•• Presents the crystal structure of wild-type ITPase and the c.94C>A variant.
  Medline CASGoogle Scholar
• 15  Arenas M, Duley J, Sumi S, Sanderson J, Marinaki A: The ITPA c.94C>A and g.IVS2+21A>C sequence variants contribute to missplicing of the ITPA gene. Biochim. Biophys. Acta1772,96–102 (2007).• Explains the molecular mechanisms associated with ITPase defiency.
  Medline CASGoogle Scholar
• 16  Heller T, Oellerich M, Armstrong VW, von Ahsen N: Rapid detection of ITPA 94C>A and IVS2 + 21A>C gene mutations by real-time fluorescence PCR and in vitro demonstration of effect of ITPA IVS2 + 21A>C polymorphism on splicing efficiency. Clin. Chem.50,2182–2184 (2004).
  Medline CASGoogle Scholar
• 17  Fraser JH, Meyers H, Henderson JF, Brox LW, McCoy EE: Individual variation in inosine triphosphate accumulation in human erythrocytes. Clin. Biochem.8,353–364 (1975).
  Medline CASGoogle Scholar
• 18  Vanderheiden BS, Bora G: Erythrocyte ITP pyrophosphohydrolase in chronic paranoid and undifferentiated schizophrenics: a biological difference. Biochem. Med.23,76–86 (1980).
  Medline CASGoogle Scholar
• 19  Duley JA, Simmonds HA, Hopkinson DA, Levinsky RJ: Inosine triphosphate pyrophosphohydrolase deficiency in a kindred with adenosine deaminase deficiency. Clin. Chim. Acta188,243–252 (1990).
  Medline CASGoogle Scholar
• 20  Mohandas T, Sparkes RS, Passage MB et al.: Regional mapping of ADA and ITP on human chromosome 20: cytogenetic and somatic cell studies in an X/20 translocation. Cytogenet. Cell Genet.26,28–35 (1980).
  Medline CASGoogle Scholar
• 21  Marsh S, King CR, Ahluwalia R, McLeod HL: Distribution of ITPA P32T alleles in multiple world populations. J. Hum. Genet.49,579–581 (2004).• Reviews the allelic frequency of ITPA c.94C>A in multiple populations.
  Medline CASGoogle Scholar
• 22  Atanasova S, Shipkova M, Svinarov D et al.: Analysis of ITPA phenotype–genotype correlation in the Bulgarian population revealed a novel gene variant in exon 6. Ther. Drug Monit.29,6–10 (2007).
  Medline CASGoogle Scholar
• 23  Maeda T, Sumi S, Ueta A et al.: Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population. Mol. Genet. Metab.85,271–279 (2005).
  Medline CASGoogle Scholar
• 24  Derijks LJ, Hommes DW: Thiopurines in inflammatory bowel disease: new strategies for optimization of pharmacotherapy? Curr. Gastroenterol. Rep.8,89–92 (2006).
  MedlineGoogle Scholar
• 25  Bakker JA, Drent M, Bierau J: Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease. Curr. Opin. Pulm. Med.13,458–463 (2007).
  MedlineGoogle Scholar
• 26  von Ahsen N, Armstrong VW, Behrens C et al.: Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study. Clin. Chem.51,2282–2288 (2005).
  Medline CASGoogle Scholar
• 27  Zelinkova Z, Derijks LJ, Stokkers PC et al.: Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin. Gastroenterol. Hepatol.4,44–49 (2006).
  Medline CASGoogle Scholar
• 28  Gearry RB, Roberts RL, Barclay ML, Kennedy MA: Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine. Pharmacogenetics14,779–781 (2004).
  Medline CASGoogle Scholar
• 29  van Dieren JM, van Vuuren AJ, Kusters JG et al.:ITPA genotyping is not predictive for the development of side effects in AZA treated inflammatory bowel disease patients. Gut54,1664 (2005).
  Medline CASGoogle Scholar
• 30  Allorge D, Hamdan R, Broly F, Libersa C, Colombel JF: ITPA genotyping test does not improve detection of Crohn’s disease patients at risk of azathioprine/6-mercaptopurine induced myelosuppression. Gut54,565 (2005).
  Medline CASGoogle Scholar
• 31  de Ridder L, van Dieren JM, van Deventer HJ et al.: Pharmacogenetics of thiopurine therapy in paediatric IBD patients. Aliment. Pharmacol. Ther.23,1137–1141 (2006).
  Medline CASGoogle Scholar
• 32  Breen DP, Marinaki AM, Arenas M, Hayes PC: Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver Transpl.11,826–833 (2005).
  MedlineGoogle Scholar
• 33  Shipkova M, Lorenz K, Oellerich M, Wieland E, von Ahsen N: Measurement of erythrocyte inosine triphosphate pyrophosphohydrolase (ITPA) activity by HPLC and correlation of ITPA genotype–phenotype in a Caucasian population. Clin. Chem.52,240–247 (2006).•• Demonstrates the correlation between ITPA genotype and ITPase activity.
  Medline CASGoogle Scholar
• 34  Lin S, McLennan AG, Ying K et al.: Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the ITPA gene. J. Biol. Chem.276,18695–18701 (2001).
  Medline CASGoogle Scholar
• 35  Kawahata RT, Chuang LF, Holmberg CA, Osburn BI, Chuang RY: Inhibition of human lymphoma DNA-dependent RNA polymerase activity by 6-mercaptopurine ribonucleoside triphosphate. Cancer Res.43,3655–3659 (1983).
  Medline CASGoogle Scholar
• 36  Zimmerman TP, Chu LC, Bugge CJ et al.: Identification of 6-methylmercaptopurine ribonucleoside 5´-diphosphate and 5´-triphosphate as metabolites of 6-mercaptopurine in man. Cancer Res.34,221–224 (1974).
  Medline CASGoogle Scholar
• 37  Nelson DJ, Bugge C, Krasny HC: Oxypurine and 6-thiopurine nucleoside triphosphate formation in human erythrocytes. Adv. Exp. Med. Biol.76A,121–128 (1977).
  Medline CASGoogle Scholar
• 38  Derijks LJ, Gilissen LP, Engels LG et al.: Pharmacokinetics of 6-mercaptopurine in patients with inflammatory bowel disease: implications for therapy. Ther. Drug Monit.26,311–318 (2004).
  Medline CASGoogle Scholar
• 39  Gilissen LP, Bierau J, Derijks LJ et al.: The pharmacokinetic effect of discontinuation of mesalazine on mercaptopurine metabolite levels in inflammatory bowel disease patients. Aliment. Pharmacol. Ther.22,605–611 (2005).
  Medline CASGoogle Scholar
• 40  Roberts RL, Gearry RB, Barclay ML, Kennedy MA: IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance. Pharmacogenomics  J. (2006) (Epub ahead of print).
  MedlineGoogle Scholar
• 41  Bierau J, Bakker JA, Lindhout M, van Gennip AH: Determination of ITPase activity in erythrocyte lysates obtained for determination of TPMT activity. Nucleosides Nucleotides Nucleic Acids25,1129–1132 (2006).
  Medline CASGoogle Scholar