NUDT15 Variation Increase the Risk of Azathioprine-induced Toxicity In Chinese Subjects:Case Report and Brief Review of the Literature
As a prodrug,azathioprine(AZA)is converted to active 6-thioguanine nucleotides(6-TGN)by an important enzyme thiopurine S-methyltransferase(TPMT).TPMT mutantion increase 6-TGN level which is thought to be associated with AZA-induced leukopenia.However,many Asian patients developed severe leukopenia even their TPMT activity is normal since the frequency of TPMT polymorphism in Asians was low.Recent studies found that NUDT15 R139C polymorphism was strongly associated with AZA-induced leukopenia in Koreans.We report a case on a Chinese Sj(o)gren”s syndrome(SS)patient with wild type TPMT suffered AZA-induced severe toxicity due to her NUDT15 variation.A 22-year-old Chinese female patient with SS developed severeleukopeniaafter taking AZA for 21 days.AZA were stopped immediately and supportive treatments were given.Detection of the 6-TGN showed the concentration in erythrocyte has beyond the reasonable monitoring range which indicted the severe leukopenia was caused by AZA.Furthermore,gene sequencing convinced that homozygous for NUDT15 R139C(poor metabolizer)was the reason to this adverse event.NUDT15 R139C and TPMT genotype are recommended to be tested to predict and prevent the AZA-induced toxicity.Moreover,6-TGN level should be monitored routinely for those who received AZA medication.
AZA NUDT15 R139C SS severe leukopenia
Xiang Fei Qing Shu Bing-zhu Hua Shi-ying Wang Zhi-yong Chen Wei-hong Ge Yun Fang
Department of Pharmacy,The Affiliated Drum Tower Hospital,Nanjing University Medical School,Nanjing, Department of Pharmacy,The Affiliated Drum Tower Hospital,Nanjing University Medical School,Nanjing, Department of Rheumatology and Immunology,The Affiliated Drum Tower Hospital,Nanjing University Medi
国内会议
西安
英文
206-211
2017-11-04（万方平台首次上网日期，不代表论文的发表时间）