AsianScientist (Jul. 20, 2018) – Researchers at Tohoku University, Japan, have found that a simple DNA test can predict if East Asian patients are likely to have bad reactions to thiopurine medications. They published their research in the Journal of Gastroenterology.
Thiopurine drugs are prescribed to patients with inflammatory bowel disease, leukemia and rheumatic disease to suppress abnormal activities of the immune system. However, some patients develop severe side effects to the drugs, including low white blood cell counts (leukopenia) and hair loss (alopecia).
There is a higher rate of severe side effects among East Asians taking thiopurines than in Caucasians, even when taking much smaller doses. Previous research had linked severe thiopurine side effects with variants of the gene that codes for the enzyme NUDT15.
In this study, researchers at Tohoku University, with collaborators from more than 30 medical centers all over Japan, screened the DNA of more than 2,600 patients with inflammatory bowel disease and compared the results with patients’ reactions to thiopurines. They found that patients were at greater risk for side effects if they had a NUDT15 gene wherein the first nucleotide of codon 139 is a cytosine.
The researchers also conducted several other genome-wide association studies to determine if any other genes should be tested to predict adverse reactions. They confirmed that it was only necessary to screen codon 139.
Based on these findings, the scientists worked with Medical and Biological Laboratories Co., Ltd. to develop a DNA sequencing kit for codon 139 that produces accurate test results within two hours. The test kit has been approved for clinical use in Japan, and the developers hope the kit will soon be available for clinical applications in other East Asian countries, such as Korea and China.
The researchers anticipate that this research and kit can help patients avoid severe side effects, and enable doctors to adjust medication levels for patients with specific variants of the NUDT15 gene. However, they note that further study is required to evaluate dosage recommendations.
The article can be found at: Kakuta et al. (2018) NUDT15 Codon 139 is the Best Pharmacogenetic Marker for Predicting Thiopurine-induced Severe Adverse Events in Japanese Patients With Inflammatory Bowel Disease: A Multicenter Study.
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Source: Tohoku University; Photo: Medical and Biological Laboratories Co., Ltd.
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