Association with HLA-DRβ1 position 37 distinguishes juvenile dermatomyositis from adult-onset myositis.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
21 07 2022
21 07 2022
Historique:
received:
10
09
2021
revised:
14
01
2022
accepted:
17
01
2022
pubmed:
31
1
2022
medline:
27
7
2022
entrez:
30
1
2022
Statut:
ppublish
Résumé
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 × 10-14], with an independent association at HLA-C*02:02 (OR = 1.74; 95% CI 1.42, 2.13, P = 7.13 × 10-8). Analyses of amino acid positions within HLA-DRB1 indicated that the strongest association was at position 37 (omnibus P = 3.3 × 10-19), with suggestive evidence this association was independent of position 74 (omnibus P = 5.1 × 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 × 10-8), but not HLA-DRB1*03:01 (OR = 1.49; 95% CR 1.24, 1.80; P = 2.24 × 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.
Identifiants
pubmed: 35094092
pii: 6517526
doi: 10.1093/hmg/ddac019
pmc: PMC9307311
doi:
Substances chimiques
Amino Acids
0
HLA-C Antigens
0
HLA-DRB1 Chains
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2471-2481Subventions
Organisme : Versus Arthritis
ID : 21552
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 085860
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR063759
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067677
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N003322/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press.
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