Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis.

Objective: To identify genetic determinants of granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: We carried out a genome-wide association study (GWAS) of 492 GPA cases and 1,506 healthy controls (white subjects of European descent), followed by replication analysis of the most strongly associated signals in an independent cohort of 528 GPA cases and 1,228 controls.

Results: Genome-wide significant associations were identified in 32 single-nucleotide polymorphic (SNP) markers across the HLA region, the majority of which were located in the HLA-DPB1 and HLA-DPA1 genes encoding the class II major histocompatibility complex (MHC) DPβ chain 1 and DPα chain 1 proteins, respectively.