ITPA genotyping test does not improve detection of Crohn’s disease patients at risk of azathioprine/6-mercaptopurine induced myelosuppression

The thiopurine drugs azathioprine (AZA) and 6-mercaptopurine (6-MP) are effective for the treatment of inflammatory bowel disease (IBD) and their prescription is increasing. Haematotoxicity, which can lead to potentially life threatening bone marrow suppression, represents the most serious side effect of thiopurine therapy. It has been attributed to the accumulation of active cytotoxic metabolites of AZA/6-MP, collectively called 6-thioguanine nucleotides, resulting from a deficiency in thiopurine catabolism specifically catalysed by the thiopurine S -methyltransferase (TPMT) enzyme. Genotyping tests are now available to identify deficient and intermediate methylators who are, respectively, homozygous and heterozygous for non-functional alleles of the TPMT gene. As pointed out by Lennard in the leading article ( Gut 2002; 51 :143–6), it is clear that myelosuppression may be caused by other factors in addition to variable TPMT. Since the identification of the molecular …

[1]  C. Vissuzaine,et al.  Fundic argyrophil carcinoid tumor in a patient with sporadic-type zollinger-ellison syndrome , 1995, Digestive Diseases and Sciences.

[2]  A. Pietrangelo.  The ferroportin disease , 2014, Clinical liver disease.

[3]  C. Lewis,et al.  Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). , 2004, Pharmacogenetics.

[4]  N. Haboubi,et al.  A novel approach to a patient with Crohn disease and a high stoma output: a missed opportunity? , 2004, Scandinavian journal of gastroenterology.

[5]  S. Sarin,et al.  Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India , 2004, Journal of gastroenterology and hepatology.

[6]  N. Mehra,et al.  Distribution of C282Y and H63D mutations in the HFE gene in healthy Asian Indians and patients with thalassaemia major. , 2003, The National medical journal of India.

[7]  M. Cazzola,et al.  Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3) , 2002, British journal of haematology.

[8]  J. Sanderson,et al.  Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency , 2002, Human Genetics.

[9]  Jennifer J. Pointon,et al.  A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4. , 2002, Blood.

[10]  L. Powell,et al.  Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis. , 2002, Blood.

[11]  M. Worwood,et al.  Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). , 2002, Blood.

[12]  J. Ironside,et al.  Creutzfeldt-Jakob disease: implications for gastroenterology , 2002, Gut.

[13]  G. Qvigstad,et al.  Neuroendocrine differentiation in gastric adenocarcinomas associated with severe hypergastrinemia and/or pernicious anemia , 2002, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[14]  S. Burden.  Dietary treatment of irritable bowel syndrome: current evidence and guidelines for future practice. , 2001, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[15]  H. Waldum,et al.  Safety of proton pump inhibitors , 2000, Alimentary pharmacology & therapeutics.

[16]  B. Bonaz,et al.  Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. , 2000, Gastroenterology.

[17]  N. Duc,et al.  Bioactive molecules in milk and their role in health and disease: The role of transforming growth factor‐β , 2000, Immunology and cell biology.

[18]  S. Hanada,et al.  Development of poorly differentiated adenocarcinoma and carcinoid due to long-term Helicobacter pylori colonization in Mongolian gerbils , 1999, Journal of Gastroenterology.

[19]  S. Falkmer,et al.  Neuroendocrine (ECL cell) differentiation of spontaneous gastric carcinomas of cotton rats (Sigmodon hispidus). , 1999, Laboratory animal science.

[20]  S. Falkmer,et al.  Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”) , 1999, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[21]  M. C. Ellis,et al.  A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis , 1996, Nature Genetics.

[22]  S. Moss,et al.  Acid secretion and sensitivity to gastrin in patients with duodenal ulcer: effect of eradication of Helicobacter pylori. , 1993, Gut.

[23]  S. Guandalini,et al.  Revised criteria for diagnosis of coeliac disease , 1990 .

[24]  M. Korman,et al.  Serum Gastrin in Chronic Gastritis , 1971, British medical journal.