Table 4.
Receptor | Polymorphism | Function/clinical association | Reference |
---|---|---|---|
FcγRIIA | Gln27Trp (rs9427397, rs9427398) |
Impaired calcium mobilization and MAP kinase phosphorylation; associated with CVID | (127) |
Gln127Lys | Gln127 interferes with the interaction of adjacent receptor residues with IgG2 | (126) | |
His131Arg (rs1801274) |
His131 able to bind IgG2; both forms associated with autoimmune disease; allograft rejection and mAb cancer treatment outcomes | (128, 129) | |
c.7421871A>G | Permits alternative splicing of the C1* exon resulting in expression of “hyperactive” FcγRIIA3. Risk factor for IVIg anaphylaxis. | (11, 12) | |
Hypomethylation | Increased susceptibility genes for Kawasaki disease and IVIg resistance | (130) | |
FcγRIIB | Promoter haplotype (rs3219018, rs34701572) |
Deregulated FcγRIIB expression may contribute to pathogenesis | (59, 131) |
Ile232Thr (rs1050501) |
Thr232 allele does not partition to lipid rafts and is associated with impaired regulation of ITAM signaling, predisposing to SLE but protective for malaria | (132–137) | |
Tyr235Asp | Asp235 has reduced binding, internalization and signaling | (95, 96) | |
FcγRIIC | Gln13stop | Commonly referred to as the ORF/Stop polymorphism, determines functional expression of receptor, may contribute to autoimmune disease | (105, 106) |
Gln57stop (rs1801274) |
Unknown mechanism, associated with autoimmune disease and vaccine efficacy for HIV | (106, 138) |