The rs150311303 Polymorphism in Fc[gamma]RIIa Enhances IgG Binding Capacity

• Published in: Scandinavian journal of immunology Vol. 76; no. 2; p. 167
• Main Authors: Omar, A H, Shibata, H, Yasunami, M, Yamazaki, A, Ofori, M F, Akanmori, B D, Shuaibu, M N, Kikuchi, M, Hirayama, K
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.08.2012
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2012.02715.x

Fc gamma receptor (Fc[gamma]R) provides an important link between humoral and cellular immune responses. Fc[gamma]RIIa-H131R polymorphism has been associated with differential binding to IgG subclasses and susceptibility to severe malaria phenotypes among different populations in the malaria endemic world. In this study, the effect of FCGR2A gene polymorphisms on susceptibility to symptomatic malaria among Ghanaian cohort children was investigated. Blood samples from four hundred and 29 (429) healthy Ghanaian children were genotyped for FCGR2A polymorphisms by direct DNA sequencing. Attributable and relative risks to symptomatic malaria were calculated for the polymorphic variants. Two major FCGR2A polymorphisms, rs1801274A/G (Fc[gamma]RIIa-H131R) and rs150311303 (Fc[gamma]RIIa-ins170L), were identified in the study population, and assessment of their risks did not show significant association with susceptibility to symptomatic malaria. The functional significance of these polymorphisms was also examined by evaluating their binding abilities to IgG subclasses using flow cytometric analysis of HEK cells transfected with the Fc[gamma]RIIa haplotype variants. The binding assay revealed the rs150311303, which was observed only among carriers of the Fc[gamma]RIIa-131RR genotype for the rs1801274 to consistently enhance binding capacities to all IgG subclasses. Thus, of the three Fc[gamma]RIIa haplotype variants observed in this study population, the Fc[gamma]RIIaRL haplotype variant was observed to have the highest binding ability to IgG1, IgG3 and IgG4. [PUBLICATION ABSTRACT]