PMID- 35120281
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220716
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 15
IP  - 5
DP  - 2022 May
TI  - HLA variants associated with azathioprine-induced pancreatitis in patients with 
      Crohn's disease.
PG  - 1249-1256
LID - 10.1111/cts.13244 [doi]
AB  - The immunosuppressant drug azathioprine is associated with a 4% risk of acute 
      pancreatitis in patients with inflammatory bowel disease (IBD). Studies have 
      demonstrated an increased risk in carriers of HLA-DQA1*02:01 and HLA-DRB1*07:01. 
      We investigated whether these human leukocyte antigen (HLA) types were associated 
      with azathioprine-induced pancreatitis also in Swedish patients with IBD, and 
      whether the type of disease affected the association. Nineteen individuals with 
      IBD who developed acute pancreatitis after initiation of azathioprine were 
      genotyped and compared with a population control cohort (n = 4891) and a control 
      group matched for disease (n = 81). HLA-DQA1*02:01 and HLA-DRB1*07:01 were in 
      full linkage disequilibrium, and were significantly associated with acute 
      pancreatitis both when cases were compared with population controls (OR 3.97 [95% 
      CI 1.57-9.97], p = 0.0035) and matched controls (OR 3.55 [95% CI 1.23-10.98], 
      p = 0.0275). In a disease-specific analysis, the correlation was positive in 
      patients with Crohn's disease versus matched controls (OR 9.27 [95% CI 
      1.86-46.19], p = 0.0066), but not in those with ulcerative colitis versus matched 
      controls (OR 0.69 [95% CI 0.07-6.74], p = 0.749). In patients with Crohn's 
      disease, we estimated the conditional risk of carriers of 
      HLA-DQA1*02:01-HLA-DRB1*07:01 to 7.3%, and the conditional risk of a non-carrier 
      to 2.2%. We conclude that HLA-DQA1*02:01-HLA-DRB1*07:01 is a marker for increased 
      risk of acute pancreatitis in individuals of Swedish genetic origin, treated with 
      azathioprine for Crohn's disease.
CI  - (c) 2022 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - As, Joel
AU  - As J
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Bertulyte, Ilma
AU  - Bertulyte I
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Eriksson, Niclas
AU  - Eriksson N
AD  - Uppsala Clinical Research Center, Uppsala, Sweden.
FAU - Magnusson, Patrik K E
AU  - Magnusson PKE
AD  - Department of Medical Epidemiology and Biostatistics, Swedish Twin Registry, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Wadelius, Mia
AU  - Wadelius M
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Hallberg, Par
AU  - Hallberg P
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220220
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*07 antigen)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Acute Disease
MH  - *Azathioprine/adverse effects
MH  - *Crohn Disease/drug therapy/genetics/immunology
MH  - *HLA-DQ alpha-Chains/genetics/immunology
MH  - *HLA-DRB1 Chains/genetics/immunology
MH  - Humans
MH  - *Inflammatory Bowel Diseases/drug therapy/immunology
MH  - *Pancreatitis/chemically induced/genetics/immunology
PMC - PMC9099136
COIS- The authors declared no competing interests for this work.
EDAT- 2022/02/05 06:00
MHDA- 2022/05/18 06:00
PMCR- 2022/05/01
CRDT- 2022/02/04 17:12
PHST- 2022/01/14 00:00 [revised]
PHST- 2021/10/14 00:00 [received]
PHST- 2022/01/20 00:00 [accepted]
PHST- 2022/02/05 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/02/04 17:12 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - CTS13244 [pii]
AID - 10.1111/cts.13244 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2022 May;15(5):1249-1256. doi: 10.1111/cts.13244. Epub 2022 Feb 
      20.