HLA allele variation as a potential explanation for the geographical distribution of granulomatosis with polyangiitis.

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.