Comprehensive Assessment of the Association between FCGRs polymorphisms and the risk of systemic lupus erythematosus: Evidence from a Meta-Analysis
SCIENTIFIC REPORTS
Authors: Zhu, Xiao-Wei; Wang, Yong; Wei, Yi-Hua; Zhao, Pian-Pian; Wang, Xiao-Bo; Rong, Jing-Jing; Zhong, Wen-Ying; Zhang, Xing-Wei; Wang, Li; Zheng, Hou-Feng
Abstract
We performed a meta analysis to assess the relationship of FCGRs polymorphisms with the risk of SLE. Thirty-five articles (including up to 5741 cases and 6530 controls) were recruited for meta-analysis. The strongest association was observed between FCGR2B rs1050501 and SLE under the recessive genotypic model of C allele in the overall population (CC vs CT/TT, OR = 1.754, 95%CI: 1.422-2.165, P = 1.61 x 10(-7)) and in Asian population (CC vs CT/TT, OR = 1.784, 95%CI; 1.408-2.261, P = 1.67 x 10(-6)). We also found that FCGR3A rs396991 were significant association with the susceptibility to SLE in overall population in recessive model of T allele (TT vs TG/GG, OR = 1.263, 95%CI: 1.123-1.421, P = 9.62 x 10(-5)). The results also showed that significant association between FCGR2A rs1801274 and SLE under the allelic model in the overall population (OR = 0.879 per A allele, 95%CI: 0.819-0.943, P = 3.31 x 10(-4)). The meta-analysis indicated that FCGR3B copy number polymorphism NA1.NA2 was modestly associated with SLE in overall population (OR = 0.851 per NA1, 95%CI: 0.772-0.938, P = 1.2 x 10(-3)). We concluded that FCGR2B rs1050501 C allele and FCGR3A rs396991 T allele might contribute to susceptibility and development of SLE, and were under recessive association model. While, FCGR2A rs1801274 A allele and FCGR3B NA1 were associated with SLE and reduced the risk of SLE.
Fc Gamma Receptor IIIB (Fc gamma RIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Children
PLOS ONE
Authors: Adu, Bright; Dodoo, Daniel; Adukpo, Selorme; Hedley, Paula L.; Arthur, Fareed K. N.; Gerds, Thomas A.; Larsen, Severin O.; Christiansen, Michael; Theisen, Michael
Abstract
Plasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub- Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB),was recently shown to correlate with protection from clinical malaria. Human neutrophils constitutively express Fc gamma receptor-Fc gamma RIIA and Fc gamma RIIIB by which they interact with immunoglobulin (Ig) G (IgG)-subclass antibodies. Polymorphisms in exon 4 of FCGR2A and exon 3 of FCGR3B genes encoding Fc gamma RIIA and Fc gamma RIIIB respectively have been described to alter the affinities of both receptors for IgG. Here, associations between specific polymorphisms, encoding Fc gamma RIIA p.H166R and Fc gamma RIIIB-NA1/NA2/SH variants with clinical malaria were investigated in a longitudinal malaria cohort study. Fc gamma RIIA-p.166H/R was genotyped by gene specific polymerase chain reaction followed by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between Fc gamma RIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C>A (rs5030738) was significantly associated with protection from clinical malaria under two out of three genetic models (additive: p = 0.0061; recessive: p = 0.097; dominant: p = 0.0076) of inheritance. The Fc gamma RIIIB-SH allotype (CTGAAA) containing the 233A-allele (in bold) was associated with protection from malaria (p = 0.049). The Fc gamma RIIIB-NA2*03 allotype (CTGCGA), a variant of the classical Fc gamma RIIIB-NA2 (CTGCAA) was associated with susceptibility to clinical malaria (p = 0.0092). The present study is the first to report an association between a variant of Fc gamma RIIIB-NA2 and susceptibility to clinical malaria and provides justification for further functional characterization of variants of the classical Fc gamma RIIIB allotypes. This would be crucial to the improvement of neutrophil mediated functional assays such as the ADRB assay aimed at assessing the functionality of antibodies induced by candidate malaria vaccines.