Do ITPA and TPMT genotypes predict the development of side effects to AZA?

• Published in: Gut 2006-07, Vol.55 (7), p.1048-1049
• Main Authors: Duley, J A, Marinaki, A M, Arenas, M, Florin, T H J
• Format: Article
• Language: English
• Subjects: azathioprine; Azathioprine - adverse effects; Crohn’s disease; Genetic Predisposition to Disease; Genotype & phenotype; genotyping; Humans; Immunosuppressive Agents - adverse effects; Inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - genetics; inosine triphosphate pyrophosphatase; Letter; Methyltransferases - genetics; Mutation; Pyrophosphatases - genetics; Studies; thiopurine methyltransferase
• ISSN: 0017-5749; 1468-3288

[...]we found an undigested band in this PCR which involved restriction endonuclease digestion that relies on creation of an Acc1 recognition site with an adequate positive (digested) control. [...]DNA sequencing by an independent laboratory also showed the wild-type genotype in the 719 site. [...]they were in the range that would require further studies before being generally accepted. 3 In fact, there are now four studies, including our own (and one upcoming) that demonstrate no significant correlation between the ITPA 94C>A polymorphism and the development of adverse drug reactions on AZA treatment. 4- 6 As with TMPT, there might be an association with homozygous ITPA 94C>A patients and thiopurine toxicity, but thus far insufficient numbers of homozygous patients have been tested to allow a firm conclusion. [...]in our minds it is to early to conclude that the ITPA 94C>A polymorphism is associated with a higher risk of the development of side effects on AZA treatment.