Analysis of the Association of AOX1 and MOCOS Polymorphisms with Azathioprine-induced Adverse Drug Reaction

doi:10.19803/j.1672-8629.2020.10.04

Abstract

Abstract: Objective To investigate the association of Aldehyde oxidase 1 (AOX1) rs55754655 and Molybdenum cofactor sulfurase (MOCOS) rs594445 polymorphisms on adverse reactions induced by azathioprine (AZA). Nucleoside diphosphate-linked moiety X-type motif 15(NUDT15) rs116855232 was been as a control site. Methods Patients who had received or were taking azathioprine were recruited to collect venous blood. Direct sequencing was used to determine the genotypes of these sites. High performance liquid chromatography was used to detect serum concentrations of AZA active metabolite 6-thioguanine nucleotide (6-TGN) in erythrocytes. Adverse drug reactions(ADRs) of these patients were monitored. Results In 80 patients, there were 2 mutant heterozygotes(AG) and no homozygous mutations with AOX1. There were 24 mutant heterozygotes(CA) and 4 homozygous mutations(AA) with MOCOS. There were 16 mutant heterozygotes(CT) and no homozygous mutations with NUDT15. Logistic regression analysis showed that the MOCOS mutation was protective for AZA-induced myelosuppression (P=0.012), and it was associated with AZA-induced flu-like symptoms and alopecia (P=0.043, 0.030). There was a significantly correlation between NUDT15 mutation and AZA-induced myelosuppression (P=0.012). There were no correlation between other ADRs and these genes mutations. There was no significant difference between wild type and mutant type of these genes in 6-TGN blood concentration(P>0.05). NUDT15 rs116855232 combined with MOCOS rs594445 analysis, patients with MOCOS wild-type and NUDT15 mutant had a higher risk of myelosuppression (OR=18.40, P=0.001). Conclusion It was suggested that MOCOS rs594445 and NUDT15 rs116855232 polymorphism should be detected bofore the first time use of AZA. It could improve the safety for using AZA.

Key words: azathioprine, aldehyde oxidase1, molybdenum cofactor sulfurase, adverse drug reaction, 6-thioguanine nucleotide

CLC Number:

R994.11

QIAN Jiajian, CHEN Chao, WANG Zhenjiang, HUANG Zaiwei, ZHANG Xiaomin, AI Xinbo. Analysis of the Association of AOX1 and MOCOS Polymorphisms with Azathioprine-induced Adverse Drug Reaction[J]. Chinese Journal of Pharmacovigilance, 2020, 17(10): 665-671.

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