Polymorphism and copy number variation ofFCGRgenes in an etiopathogenesis of sarcoidosis

Background: The immunocomplexemia in our patients with Stage I/II of sarcoidosis (SA), not with Stage III/IV, may be a result of phagocytes9 disorder of abilities in clearance of immune complexes (CIs), which rely on the function of receptors for Fc fragment of IgG (FcγR). However, we revealed increased FcγRs9 expression on phagocytes in the same SA patients. It may point to a lowered affinity of FcγRs to CIs due to a polymorphism and/or copy number variation (CNV) of FCGR genes, encoding FcγRs. Aim/Materials/Methods: Thus, we analyzed polymorphism and CNV of FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCGR3B genes in 124 SA patients and 148 healthy volunteers (C) using PCR-SSP and Real-Time PCR. Results: We revealed significantly lower percentage of FCGR2A and FCGR2C with more functional variants of these genes in Stages I/II vs. III/IV of SA. Moreover, the V158F polymorphism of FCGR3A , responsible for a decreased affinity of FcγRIIIa to CIs and their decreased clearance was increased in Stage I vs. Stage II and C. There was no aberration in FCGR2B and FCGR3B variants, as well in CNV of tested genes between SA or its stages and C, as well as between stages themselves. We only detected a relevant increase in CNV of FCGR2C and FCGR3B in Stage IV of SA vs. other stages and C, but a broader study is needed to verify this. Conclusions: Thus, FCGR2A, FCGR2C and FCGR3A polymorphism may contribute to immunocomplexemia present in SA. The assessment of FCGR genes could become a tool in presaging a clinical course of SA and in its personalized therapy. CNV of FCGR genes seems to be less important than FCGR polymorphism in the etiopathogenesis of SA in our patients. Support by grants: 5160/B/P01/2010/39 and 02-0127/07/232.