gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease
| Title: | gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease |
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| Authors: | Katsuyoshi Matsuoka |
| Source: | Intestinal Research, Vol 18, Iss 3, Pp 275-281 (2020) |
| Publisher Information: | Korean Association for the Study of Intestinal Diseases, 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Medicine LCC:Diseases of the digestive system. Gastroenterology |
| Subject Terms: | nudt15, thiopurine, azathioprine, 6-mercaptopurine, Medicine, Diseases of the digestive system. Gastroenterology, RC799-869 |
| More Details: | Thiopurine has been used to maintain remission and to reduce antidrug antibody formation in monoclonal antibody therapy in patients with inflammatory bowel disease (IBD). The use of thiopurine is limited by side effects such as leukopenia. Thiopurine S-methyltransferase (TPMT) variants are associated with thiopurine-induced leukopenia in Westerners, but the frequency of the risk alleles is low in Asians. Recently, a variant in the nudix hydrolase 15 (NUDT15) gene (R139C, c.415C > T) was reported to be associated with early severe leukopenia in Asians. NUDT15 is an enzyme that converts 6-thio-(deoxy)guanosine triphosphate (6-T(d)GTP) to 6-thio-(deoxy)guanosine monophosphate (6-T(d)GMTP). The R139C variant impairs the stability of the protein and increases incorporation of 6-TGTP and 6-TdGTP into RNA and DNA, respectively, resulting in leukopenia. The frequency of C/C, C/T, and T/T are approximately 80%, 20%, and 1%, respectively in East Asians. Early leukopenia occurred in less than 3% of patients with C/C and in around 20% of those with C/T, whereas it occurred in almost all patients with T/T. Patients homozygous for this variant also develop severe hair loss. The measurement of NUDT15 R139C can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of IBD. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1598-9100 2288-1956 |
| Relation: | http://www.irjournal.org/upload/pdf/ir-2020-00002.pdf; https://doaj.org/toc/1598-9100; https://doaj.org/toc/2288-1956 |
| DOI: | 10.5217/ir.2020.00002 |
| Access URL: | https://doaj.org/article/f41a06260d794c4b8cb0dbe53ab88803 |
| Accession Number: | edsdoj.f41a06260d794c4b8cb0dbe53ab88803 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15989100 22881956 |
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| DOI: | 10.5217/ir.2020.00002 |
| Published in: | Intestinal Research |
| Language: | English |