A trend toward increased frequency of DPB1*04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1*13:02 (Padjusted = 0.0021, ORadjusted = 3.48).
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.
In addition, these studies have also shown that different AAV subtypes such as granulomatosis with polyangiitis (Wegener's, GPA) and microscopic polyangiitis (MPA) are underpinned by distinct genetic risk factors, with GPA being associated with HLA-DP, SERPINA1 (encoding α1-antitrypsin), PRTN3 (encoding proteinase-3, PR3, the main GPA-related autoantigen) and SEMA6A (semaphorin 6A), whereas MPA has been mainly associated with HLA-DQ.
HLA-DPB1, the association of which with Wegener's granulomatosis has been discovered some years ago, is still the strongest and best replicated risk locus for this condition.
The previously reported strong association of WG with the HLA-DPB1*0401 allele was confirmed in an independent WG sample (n = 108, p(c) = 6.4 x 10(-8)).