P152 The prevalence of Thiopurine-methyltransferase and NUTD15 in patient with ulcerative colitis: a hospital-based study in central Taiwan
Wu, Y.H.(1)*;Chou, J.W.(2);Po, J.H.(1);Wang, C.P.(1); Cheng, K.S.(1);
(1)China Medical University Hospital, Center for Digestive Medicine- Department of Internal Medicine, Taichung, Taiwan;(2)China Medical University Hospital, Department of Internal Medicine, Taichung City, Taiwan;
Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of these thiopurine drugs. Methylation of thiopurine drugs by TPMT competes with the formation of their active 6-thioguanine nucleotide metabolite, thereby potentially modulating the therapeutic and toxic effects of these drugs. Polymorphisms in TPMT and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine-induced leukopenia in the Western and East Asian countries, but the frequency of the risk alleles is lower in Asians. Recently, a variant in the NUDT15 was reported to be associated with early severe leukopenia in Asians. The exact role of these polymorphisms in patients with ulcerative colitis (UC) in Taiwan is uncertain.
The aim of this study was to investigate the prevalence of TPMT and NUDT 15 variants and other characteristics in patients with UC in central Taiwan.
From January 1980 to November 2022, a total of 172 consecutive patients with UC at the China Medical University Hospital, a tertiary referral center in central Taiwan, were enrolled in this study. Clinical characteristics of patients with UC, including gender, age at diagnosis, disease phenotype and behavior, were collected. We used polymerase chain reaction-restriction fragment length polymorphism method to determine the allelic frequencies of TPMT and NUD15 variants in our UC patients.
A total of 172 patients with UC was enrolled into our current study. The mean diagnostic age of these enrolled patients was 46.1 years (ranging from 21 years to 75 years old). Male accounted for the majority of all patients in our present study (64.5%). Among these 172 patients with UC, TPMT variants were tested in 138 patients, which showed the allelic frequencies of TPMT*1 were 98.5% (136/138) for patients with UC. The allelic frequencies of TPMT*3C were 1.5% (2/138) for patients with UC. No TPMT*2, 3A, 3B, 3D and 4-8 were found in these populations. In addition, NUD15 was tested in 123 patients with UC, which showed normal metabolizer in 109 patients (88.6%, 109/123), intermediate metabolizer in 14 patients (11.4%, 14/123), and poor metabolizer in 0 patient (0%, 0/123).
NUDT15 mutation rate was significantly higher than TPMT polymorphism and reached 11.4%. NUDT15 mutation was associated with thiopurine-induced leukopenia. The measurement of NUDT15 polymorphism can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of UC. Phenotypic TPMT and NUDT15 analysis could be useful to better manage UC therapy with thiopurine.