P723 NUDT15 R139C genotype is a determinant of thiopurines-induced leukopenia in Chinese patients with Crohn’s disease
X. Zhu1, K. Chao*2, X. Wang1, P. Hu2, M. Huang1, X. Gao2
1Sun Yat-Sen University, School of Pharmaceutical Sciences, Guangzhou, China, 2The Sixth Affiliated Hospital, Sun Yat-sen University, Gastroenterology and Hepatology, Guangzhou, China
The incidence of thiopurine-induced leukopenia is higher in Asians than in individuals of European descent, but the predictability based on TPMT genotype is limited, especially in Asian patients. NUDT15 R139C was recently proposed to be a promising pharmgenetic marker for thiopurine therapy, which was not replicated in Chinese population. The aim of the present study was to investigate the influence of NUDT15 R139C genotypes on thiopurine-induced adverse effects in Chinese patients with Crohn’s disease.
A single-centre study was conducted in the Department of Gastroenterology of The Sixth Affiliated Hospital, Sun Yat-sen University. The Crohn’s disease (CD) patients with standard dose of thiopurine for more than 1 week were recruited. Clinical and epidemiological characteristics were collected from the IBD database of our centre. NUDT15 R139C genotypes were determined with PCR-RFLP. The interactions between gene and adverse effects were analysed.
In total, 253 Chinese CD patients were included. Amongst them, 65 (25.7%) developed leukopenia. There was significant association of NUDT15 R139C and thiopurine-induced leukopenia (P = 7.65*10–17). Further, 36 patients (36/53, 67.9%) with heterozygous for NUDT15 R139C developed leukopenia, 4 (1.6%) patients with mutant homozygous (T/T), and all of them (100%) developed early leukopenia (< 1 month) and severe hair loss, whereas only 12.8% (25/196) of patients with C/C genotype of NUDT15 R139C developed leukopenia. Compared with the wide-type homozygotes (CC), patients carrying variant allele T (CT+TT) have much higher risk for leukopenia (p = 2.48*101– 8, OR = 16.09, 95% CI 7.95–32.60).
NUDT15 R139C could be a promising biomarker for thiopurine-induced leukopenia in Chinese patients with IBD. Multicentre study should be done to verify our findings and further clarify the molecular mechanisms.