A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 ( IRF5 ), major histocompatibility complex ( MHC ), tumor necrosis factor (ligand) superfamily member 4 ( TNFSF4 ), Kell blood group complex subunit-related family member 6 ( XKR6 ), B-cell scaffold protein with ankyrin repeats 1 ( BANK1 ), protein tyrosine phosphatase non-receptor type 22 ( PTPN22 ), ubiquitin-conjugating enzyme E2L 3 ( UBE2L3 ) and islet cell autoantigen 1 ( ICA1 ). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 ( CTLA4 ), a gene associated with several autoimmune disorders, and ERBB3 , a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.