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The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population

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Názov: The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population
Autori: Lundtoft, Christian, Knight, Ann, Meadows, Jennifer R S, Karlsson, Åsa, Rantapää-Dahlqvist, Solbritt, Berglin, Ewa, Palm, Øyvind, Haukeland, Hilde, Gunnarsson, Iva, Bruchfeld, Annette, Segelmark, Mårten, Ohlsson, Sophie, Mohammad, Aladdin J, Eriksson, Per, Söderkvist, Peter, Ronnblom, Lars, Omdal, Roald, Jonsson, Roland, Lindblad-Toh, Kerstin, Dahlqvist, Johanna
Prispievatelia: Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section II, Nephrology, Autoimmunity and kidney diseases, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion II, Njurmedicin, Autoimmunitet och njursjukdomar, Originator, Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Rheumatology, Lund Vasculitis Epidemiology Research Group, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Reumatologi och molekylär skelettbiologi, Lund Vasculitis Epidemiology Research Group, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Orthopaedics (Lund), Lund OsteoArthritis Division - Clinical Epidemiology Unit, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Ortopedi, Lund, Lund OsteoArthritis Division - Clinical Epidemiology Unit, Originator
Zdroj: RMD Open. 10(2):1-10
Predmety: Medical and Health Sciences, Basic Medicine, Medical Genetics and Genomics (including Gene Therapy), Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik och genomik (Här ingår: Genterapi)
Popis: 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*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 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.
Prístupová URL adresa: https://doi.org/10.1136/rmdopen-2023-004039
Databáza: SwePub
Popis
Abstrakt: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*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 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.
ISSN:20565933
DOI:10.1136/rmdopen-2023-004039