FCGR2B and FCRLB Gene Polymorphisms Associated with IgA Nephropathy

Background: IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (Fc gamma Rs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort. Patients and Methods: 60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese. Results: Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.74*10(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p = 2.28*10(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65 x 10(-2)) as well as gross hematuria (p = 4.53 x 10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67 x 10(-2)) as well as eGFR (p = 5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions. Conclusion: Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.