Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA.

ABSTRACT:

Objective

To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV).

Methods

Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay.

Results

PR3-ANCA+ AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 × 10-61, odds ratio (OR) 0.10; rs9277341, P = 1.5 × 10-44, OR 0.2

SUBMITTER: Dahlqvist J 

PROVIDER: S-EPMC9348767 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature