HLA-DPB1 variant rs3117242 is associated with anti-neutrophil cytoplasmic antibody-associated vasculitides in a Han...

The vasculitis diseases granulomatosis with polyangiitis (GPA) and microscopic polyangitis (MPA) are the two major forms of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). A recent genome-wide association study has shown that the genes HLA-DPB1 and HLA-DQ conferred susceptibility to GPA and MPA, respectively. We investigated the linkage between putative AAV-related genes (HLA-DPB1, ARHGAP18, CD226, CTLA-4, MOSPD2 and PRTN3) and AAV in a Han Chinese population.

A Sequenom MassAarray system (iPLEX assay, Sequenom, San Diego, CA, USA) was used to genotype single nucleotide polymorphisms (SNPs) in 176 Han Chinese patients with AAV (100 with GPA, 76 with MPA) and 485 ethnically matched healthy controls.

The frequency of the rs3117242 variant T allele (HLA-DPB1) was significantly higher in GPA patients than in the controls (68.0% compared with 50.4%, OR = 2.09, 95% CI: 1.51-2.88, Bonferroni corrected P-value [Pc] = 6.24E-5), but was not significantly different between MPA patients and controls (Pc = 0.14). The same results were obtained via genotype distribution and logistic regression analysis based on three genetic models. The allele and genotype distributions of the other polymorphisms were not significantly associated with AAV patients as a whole or GPA or MPA patients considered separately.

The rs3117242 of HLA-DPB1 could be considered a genetic risk factor for GPA in Chinese Han people. These findings provide further insights and clues into the etiology of GPA and MPA.