The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population.
RMD Open
; 10(2)2024 Apr 04.
Article
em En
| MEDLINE
| ID: mdl-38580345
ABSTRACT
OBJECTIVE:
The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS:
Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS:
PR3-AAV was significantly associated with both HLA-DPB1*0401 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*0404. Neither carriage of HLA-DPB1*0401 alleles in PR3-AAV nor of HLA-DRB1*0404 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse.CONCLUSIONS:
The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Anticitoplasma de Neutrófilos
/
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
RMD Open
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suécia