Richard A Watts1, Alex J MacGregor2, Sarah L Mackie2. 1. Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, Norwich Medical School, University of East Anglia, Norwich and School of Medicine and NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, UK. Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, Norwich Medical School, University of East Anglia, Norwich and School of Medicine and NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, UK. richard.watts@ipswichhospital.nhs.uk. 2. Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, Norwich Medical School, University of East Anglia, Norwich and School of Medicine and NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, UK.
Abstract
OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune systemic vasculitis considered to result from the interaction of environmental factors with a genetically predisposed host. The HLA-DPB1*0401 allele, the PI*Z allele of the gene encoding α1-antitrypsin (SERPINA1) and the proteinase 3 (PRTN3) gene have been associated with GPA. The incidence of GPA is lower in non-Caucasian populations and has been associated with higher latitude. Our aim was to determine whether variation in population carrier frequency of the HLA-DPB1*0401 and PI*Z alleles could explain in part the variation in GPA incidence between countries. METHODS: We systematically identified published reports on the incidence of GPA and used previously published data on the frequency of HLA-DBP1*0401 and PI*Z alleles. The relationship between GPA incidence, latitude and population HLA-DPB1*0401 and PI*Z allele frequencies was assessed by linear regression. RESULTS: On multivariate analysis GPA incidence was associated with HLA-DPB1*0401 allele frequency (P = 0.001) but not with PI*Z allele frequency or latitude. CONCLUSION: HLA-DPB1*0401 is a GPA susceptibility allele and HLA-DPB1*0401 population allele frequencies may help explain variations in GPA incidence described in the literature.
OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune systemic vasculitis considered to result from the interaction of environmental factors with a genetically predisposed host. The HLA-DPB1*0401 allele, the PI*Z allele of the gene encoding α1-antitrypsin (SERPINA1) and the proteinase 3 (PRTN3) gene have been associated with GPA. The incidence of GPA is lower in non-Caucasian populations and has been associated with higher latitude. Our aim was to determine whether variation in population carrier frequency of the HLA-DPB1*0401 and PI*Z alleles could explain in part the variation in GPA incidence between countries. METHODS: We systematically identified published reports on the incidence of GPA and used previously published data on the frequency of HLA-DBP1*0401 and PI*Z alleles. The relationship between GPA incidence, latitude and population HLA-DPB1*0401 and PI*Z allele frequencies was assessed by linear regression. RESULTS: On multivariate analysis GPA incidence was associated with HLA-DPB1*0401 allele frequency (P = 0.001) but not with PI*Z allele frequency or latitude. CONCLUSION: HLA-DPB1*0401 is a GPA susceptibility allele and HLA-DPB1*0401 population allele frequencies may help explain variations in GPA incidence described in the literature.
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