Identification of susceptibility locus shared by IgA nephropathy and inflammatory bowel disease in a Chinese Han population

Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13–1.45, P = 1.42 × 10 −4 ) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus ( CFB ) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.