In recent years, there has been renewed interest in the role of IgG in intestinal immunity, driven in part by a genetic association of an affinity-lowering variant of an IgG receptor, FcγRIIA, with protection from ulcerative colitis (UC), a subclass of inflammatory bowel disease (IBD).
Specifically, a variant of the activating receptor, FcγRIIA, with low affinity for IgG, confers protection against the development of ulcerative colitis, a subset of IBD, leading to a re-evaluation of the role of IgG and FcγRs in gastrointestinal tract immunity, an organ system traditionally associated with IgA.
Genome-wide association studies (GWASs) in UC implicate a FCGR2A variant that alters the binding affinity of the antibody receptor it encodes, FcγRIIA, for immunoglobulin G (IgG).
The TC haplotype constructed by the major allele of FCGR2A (rs1801274 and rs511278) was more prevalent in UC patients compared with controls (65.2% vs. 60.2%, p = 0.017).
Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.
We confirmed the associations of 10 known UC risk loci in Koreans: rs76418789 in IL23R (combined P = 1.25 × 10), rs4728142 in IRF5 (combined P = 3.17 × 10), rs1830610 near JAK2 (combined P = 2.28 × 10), rs1555791 near TNFRSF14 (combined P = 1.62 × 10), rs880790 between IL10-IL19 (combined P = 3.73 × 10), rs10185424 between IL1R2-IL1R1 (combined P = 1.54 × 10), rs6478108 in TNFSF15 (combined P = 9.28 × 10), rs861857 between UBE2L3-YDJC (combined P = 3.05 × 10), rs1801274 in FCGR2A (discovery P = 1.54 × 10), and rs17085007 between GPR12-USP12 (discovery P = 3.64 × 10).
After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3).
After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3).