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Comparison of and polymorphisms in Chinese patients with inflammatory bowel disease.

World J Gastroenterol; 24(8): 941-948, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29491687

AIM:

To observe gene polymorphisms of and , and compare their predictive value for azathioprine (AZA)-induced leukopenia in inflammatory bowel disease (IBD).

METHODS:

This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of and by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Eighty patients were treated with AZA according to the disease condition. During the first month, patients who received AZA underwent routine blood tests and liver function tests once a week. The endpoint of the study was leukopenia induced by AZA. By analyzing patient characteristics, genotypes and leukopenia induced by drug use, we found the risk factors associated with AZA-induced leukopenia.

RESULTS:

There were 219 patients with IBD (160 men and 59 women), including 39 who were confirmed with ulcerative colitis (UC), 176 with Crohn's disease (CD) and 4 with undetermined IBD (UIBD). There were 44 patients (20.1%) with mutant genotype of (C/T); among them, 16 received AZA, and 8 (50%) developed leukopenia. There were 175 patients (79.7%) with wild genotype of (C/C); among them, 64 received AZA, and 11 (17.2%) developed leukopenia. A significant difference was found between C/T and its wild-type C/C ( = 0.004). There were only 3 patients with mutant genotype of A/G (1.4%) who participated in the research, and 1 of them was treated with AZA and developed leukopenia. The remaining 216 patients (98.6%) were found to bear the wild genotype of (A/A); among them, 79 patients received AZA, and 18 (22.8%) developed leukopenia, and there was no significant difference from those with A/G ( = 0.071). The frequency of mutation was 1.4%, and mutation rate was significantly higher and reached 20.1% ( = 0.000). Therefore, gene polymorphism was obviously a better biomarker than gene polymorphism in the prediction of AZA-induced leukopenia.

CONCLUSION:

Mutation rate of in Chinese IBD patients is higher than that of . polymorphism is a better predictor for AZA-induced leukopenia than polymorphism.