gene test must for ibd patients for drug tolerance

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Scientists at Hinduja Hospital, Mahim, have established a link between gene mutation and increased toxicity induced by a group of drugs that treat inflammation in bowels and large intestine.Of the 69 patients with inflammatory bowel disorders (IBD) that were observed, 34 suffered from Ulcerative Colitis, 24 from Crohn’s disease, and 11 from auto-immune disorder related to hepatitis. The patients were on Thiopurine drugs, and six of them developed complications due to toxic effects of the drugs.

            “Six patients, that is 8.7 per cent, developed Thiopurine-induced toxicity, and their white blood cell (WBC) count dropped below 3,000 cubic millimetres. In one patient, the reaction was so serious, that the WBC count dropped drastically in over a day,” said Dr Swarup Shah, Molecular Scientist, PD Hinduja Hospital. “We either had to reduce drug dosage or stop the drug altogether, so that the condition does not become lethal,” he said. A normal WBC count ranges between 4,000 to 10,000 cubic millimetre.

        In case of IBDs, body’s own immunity attacks the intestines, causing ulcers and sores. Patients are in extreme pain due to constant symptoms of dysentery and passing blood in stools, and require long-term medication.All 69 patients were tested for NUTD15 (nucleoside diphosphate-linked moiety X-type motif 15) and TMPT (thiopurine methyltransferase) gene mutation. NUTD15 and TMPT genes help in metabolising Thiopurine drugs. “US FDA (Food and Drug Administration) guidelines suggest that patients undergo TMPT gene test to check if they are vulnerable to toxic effects of the drug. However, effects of NUTD15 gene mutation have not been studied,” said Dr Tester Ashavaid, Head, Lab Medicine at the hospital.

After genotyping, they found nine had mutated NUTD15 gene, and six patients developed toxicity to the drug. Studies in Japanese, Korean, Thai and Taiwanese populations have shown a similar trend. “We insist that patients are tested for NUTD15 gene mutation before being put on Thiopurines. The Asia-Pacific region needs separate guidelines; we cannot rely on US-FDA guidelines,” said Dr Shah.
Thiopurine drug toxicity due to NUTD 15 gene mutation is unique to Indians and unheard of in Europeans and Americans, said Mumbai scientists