title: HLA allele variation as a potential explanation for the geographical distribution of granulomatosis with polyangiitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Watts
authors.affiliation: 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.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: MacGregor
authors.affiliation: 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.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Mackie
mesh_terms: D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D062306:Geography, Medical; D014943:Global Health; D014890:Granulomatosis with Polyangiitis / Q000453:epidemiology / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006801:Humans; D015994:Incidence; D015999:Multivariate Analysis
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen
keywords: HLA; epidemiology; genetics; granulomatosis with polyangiitis; vasculitis