PMID- 29702976
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20210212
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 17
DP  - 2018 Apr
TI  - NUDT15 R139C variation increases the risk of azathioprine-induced toxicity in 
      Chinese subjects: Case report and literature review.
PG  - e0301
LID - 10.1097/MD.0000000000010301 [doi]
LID - e0301
AB  - INTRODUCTION: Azathioprine (AZA) is widely used as an immunosuppressive agent, 
      and its efficacy has been recommended by many clinical studies. However, 
      leukopenia, the most common toxicity, still restricts its clinical applications. 
      Recent studies found that NUDT15 R139C polymorphism is strongly associated with 
      AZA-induced leukopenia in Koreans. However, the follow-up studies available are 
      all limited to inflammatory bowel disease (IBD). Here, we report a case of a 
      Chinese patient with Sjogren syndrome (SS) with wild-type TPMT*3C who was 
      diagnosed with AZA-induced severe toxicity due to NUDT15 mutation based on 
      clinical and laboratory characteristics. CASE PRESENTATION: A 22-year-old Chinese 
      woman with SS developed severe leukopenia after AZA administration for 21 days. 
      Detection of 6-thioguanine nucleotides (6-TGN) showed that the erythrocyte 
      concentration had beyond the monitoring range, indicating that severe leukopenia 
      might be caused by AZA. Furthermore, gene sequencing showed that NUDT15 R139C 
      (poor metabolizer) homozygosity might explain this adverse event. Based on the 
      evidence, AZA administration was immediately stopped and supportive treatments 
      provided, and the patient eventually recovered. CONCLUSION: In this report, we 
      first provide detailed clinical and laboratory characteristics of AZA-induced 
      leukopenia in a patient with SS with a mutant NUDT15 R139C genotype (TT allele) 
      and normal TPMT activity. This case indicates that NUDT15 R139C and TPMT*3C 
      genotypes, and more importantly, 6-TGN levels, should be routinely monitored for 
      those administered with AZA to predict and prevent AZA-induced toxicity.
FAU - Fei, Xiang
AU  - Fei X
AD  - Department of Pharmacy, The Affiliated Drum Tower Hospital, Nanjing University 
      Medical School.
AD  - School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University.
FAU - Shu, Qing
AU  - Shu Q
AD  - Department of Pharmacy, The Affiliated Drum Tower Hospital, Nanjing University 
      Medical School.
FAU - Hua, Bing-Zhu
AU  - Hua BZ
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Nanjing University Medical School, Nanjing, China.
FAU - Wang, Shi-Ying
AU  - Wang SY
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Nanjing University Medical School, Nanjing, China.
FAU - Chen, Zhi-Yong
AU  - Chen ZY
AD  - Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, 
      Nanjing University Medical School, Nanjing, China.
FAU - Ge, Wei-Hong
AU  - Ge WH
AD  - Department of Pharmacy, The Affiliated Drum Tower Hospital, Nanjing University 
      Medical School.
FAU - Fang, Yun
AU  - Fang Y
AD  - Department of Pharmacy, The Affiliated Drum Tower Hospital, Nanjing University 
      Medical School.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.67 (thiopurine methyltransferase)
RN  - EC 2.6.1.- (NUDT15 protein, human)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Azathioprine/*pharmacokinetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Methyltransferases/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Pyrophosphatases/*genetics
MH  - Sjogren's Syndrome/*genetics
MH  - Young Adult
PMC - PMC5944482
COIS- The authors have no conflicts of interest to disclose.
EDAT- 2018/04/29 06:00
MHDA- 2018/05/15 06:00
PMCR- 2018/04/27
CRDT- 2018/04/29 06:00
PHST- 2018/04/29 06:00 [entrez]
PHST- 2018/04/29 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2018/04/27 00:00 [pmc-release]
AID - 00005792-201804270-00008 [pii]
AID - MD-D-17-07689 [pii]
AID - 10.1097/MD.0000000000010301 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Apr;97(17):e0301. doi: 10.1097/MD.0000000000010301.