PMID- 35094092
OWN - NLM
STAT- MEDLINE
DCOM- 20220726
LR  - 20221013
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 31
IP  - 14
DP  - 2022 Jul 21
TI  - Association with HLA-DRbeta1 position 37 distinguishes juvenile dermatomyositis from 
      adult-onset myositis.
PG  - 2471-2481
LID - 10.1093/hmg/ddac019 [doi]
AB  - Juvenile dermatomyositis (JDM) is a rare, severe autoimmune disease and the most 
      common idiopathic inflammatory myopathy of children. JDM and adult-onset 
      dermatomyositis (DM) have similar clinical, biological and serological features, 
      although these features differ in prevalence between childhood-onset and 
      adult-onset disease, suggesting that age of disease onset may influence 
      pathogenesis. Therefore, a JDM-focused genetic analysis was performed using the 
      largest collection of JDM samples to date. Caucasian JDM samples (n = 952) 
      obtained via international collaboration were genotyped using the Illumina 
      HumanCoreExome chip. Additional non-assayed human leukocyte antigen (HLA) loci 
      and genome-wide single-nucleotide polymorphisms (SNPs) were imputed. 
      HLA-DRB1*03:01 was confirmed as the classical HLA allele most strongly associated 
      with JDM [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.46, 1.89; 
      P = 1.4 x 10-14], with an independent association at HLA-C*02:02 (OR = 1.74; 95% 
      CI 1.42, 2.13, P = 7.13 x 10-8). Analyses of amino acid positions within HLA-DRB1 
      indicated that the strongest association was at position 37 (omnibus 
      P = 3.3 x 10-19), with suggestive evidence this association was independent of 
      position 74 (omnibus P = 5.1 x 10-5), the position most strongly associated with 
      adult-onset DM. Conditional analyses also suggested that the association at 
      position 37 of HLA-DRB1 was independent of some alleles of the Caucasian HLA 8.1 
      ancestral haplotype (AH8.1) such as HLA-DQB1*02:01 (OR = 1.62; 95% CI 1.36, 1.93; 
      P = 8.70 x 10-8), but not HLA-DRB1*03:01 (OR = 1.49; 95% CR 1.24, 1.80; 
      P = 2.24 x 10-5). No associations outside the HLA region were identified. Our 
      findings confirm previous associations with AH8.1 and HLA-DRB1*03:01, HLA-C*02:02 
      and identify a novel association with amino acid position 37 within HLA-DRB1, 
      which may distinguish JDM from adult DM.
CI  - (c) The Author(s) 2022. Published by Oxford University Press.
FAU - Deakin, Claire T
AU  - Deakin CT
AUID- ORCID: 0000-0002-7044-5801
AD  - Infection, Immunity and Inflammation Research and Teaching Department, UCL Great 
      Ormond Street Institute of Child Health, London, UK.
AD  - Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCL Hospital and 
      Great Ormond Street Hospital, London, UK.
AD  - NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
FAU - Bowes, John
AU  - Bowes J
AD  - Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, Manchester Academic Health Science Centre, The University of 
      Manchester, Manchester, UK.
AD  - National Institute of Health Research Manchester Biomedical Research Centre, 
      Manchester Academic Health Science Centre, Manchester University NHS Foundation 
      Trust, Manchester, UK.
FAU - Rider, Lisa G
AU  - Rider LG
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA.
FAU - Miller, Frederick W
AU  - Miller FW
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA.
FAU - Pachman, Lauren M
AU  - Pachman LM
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of 
      Medicine, Northwestern University, Chicago, IL, USA.
FAU - Sanner, Helga
AU  - Sanner H
AD  - Department of Rheumatology, University of Oslo, Oslo, Norway.
AD  - Oslo New University College, Oslo, Norway.
FAU - Rouster-Stevens, Kelly
AU  - Rouster-Stevens K
AD  - Emory University School of Medicine, Atlanta, GA, USA.
FAU - Mamyrova, Gulnara
AU  - Mamyrova G
AD  - Division of Rheumatology, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Curiel, Rodolfo
AU  - Curiel R
AD  - Division of Rheumatology, George Washington University School of Medicine and 
      Health Sciences, Washington, DC, USA.
FAU - Feldman, Brian M
AU  - Feldman BM
AD  - Division of Rheumatology, Department of Pediatrics, The Hospital for Sick 
      Children, Toronto, ON, Canada.
FAU - Huber, Adam M
AU  - Huber AM
AD  - IWK Health Centre and Dalhousie University, Halifax, NS, Canada.
FAU - Reed, Ann M
AU  - Reed AM
AD  - Pediatrics, Duke University, Durham, NC, USA.
FAU - Schmeling, Heinrike
AU  - Schmeling H
AD  - Department of Pediatrics, Alberta Children's Hospital, University of Calgary, 
      Calgary, AB, Canada.
FAU - Cook, Charlotte G
AU  - Cook CG
AD  - Infection, Immunity and Inflammation Research and Teaching Department, UCL Great 
      Ormond Street Institute of Child Health, London, UK.
FAU - Marshall, Lucy R
AU  - Marshall LR
AD  - Infection, Immunity and Inflammation Research and Teaching Department, UCL Great 
      Ormond Street Institute of Child Health, London, UK.
AD  - Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCL Hospital and 
      Great Ormond Street Hospital, London, UK.
AD  - NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
FAU - Ll Wilkinson, Meredyth G
AU  - Ll Wilkinson MG
AD  - Infection, Immunity and Inflammation Research and Teaching Department, UCL Great 
      Ormond Street Institute of Child Health, London, UK.
AD  - Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCL Hospital and 
      Great Ormond Street Hospital, London, UK.
AD  - NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
FAU - Eyre, Stephen
AU  - Eyre S
AD  - Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, Manchester Academic Health Science Centre, The University of 
      Manchester, Manchester, UK.
AD  - National Institute of Health Research Manchester Biomedical Research Centre, 
      Manchester Academic Health Science Centre, Manchester University NHS Foundation 
      Trust, Manchester, UK.
FAU - Raychaudhuri, Soumya
AU  - Raychaudhuri S
AD  - Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal 
      Research, Manchester Academic Health Science Centre, The University of 
      Manchester, Manchester, UK.
AD  - National Institute of Health Research Manchester Biomedical Research Centre, 
      Manchester Academic Health Science Centre, Manchester University NHS Foundation 
      Trust, Manchester, UK.
AD  - Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
FAU - Wedderburn, Lucy R
AU  - Wedderburn LR
AD  - Infection, Immunity and Inflammation Research and Teaching Department, UCL Great 
      Ormond Street Institute of Child Health, London, UK.
AD  - Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCL Hospital and 
      Great Ormond Street Hospital, London, UK.
AD  - NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, UK.
CN  - Juvenile Dermatomyositis Cohort and Biomarker Study, the Childhood Myositis 
      Heterogeneity Study Group, and the Myositis Genetics Consortium (MYOGEN)
LA  - eng
GR  - 21552/VAC_/Versus Arthritis/United Kingdom
GR  - 085860/WT_/Wellcome Trust/United Kingdom
GR  - R01 AR063759/AR/NIAMS NIH HHS/United States
GR  - UH2 AR067677/AR/NIAMS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - MR/N003322/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Amino Acids)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Amino Acids/genetics
MH  - Child
MH  - *Dermatomyositis/diagnosis/genetics
MH  - Genetic Predisposition to Disease
MH  - HLA-C Antigens/genetics
MH  - *HLA-DRB1 Chains/genetics
MH  - Haplotypes/genetics
MH  - Humans
MH  - *Myositis/diagnosis/genetics
PMC - PMC9307311
EDAT- 2022/01/31 06:00
MHDA- 2022/07/27 06:00
PMCR- 2022/01/31
CRDT- 2022/01/30 20:37
PHST- 2021/09/10 00:00 [received]
PHST- 2022/01/14 00:00 [revised]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/01/31 06:00 [pubmed]
PHST- 2022/07/27 06:00 [medline]
PHST- 2022/01/30 20:37 [entrez]
PHST- 2022/01/31 00:00 [pmc-release]
AID - 6517526 [pii]
AID - ddac019 [pii]
AID - 10.1093/hmg/ddac019 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2022 Jul 21;31(14):2471-2481. doi: 10.1093/hmg/ddac019.