TY - JOUR
T1 - The rs150311303 polymorphism in FcγRIIa enhances IgG binding capacity
AU - Omar, A. H.
AU - Shibata, H.
AU - Yasunami, M.
AU - Yamazaki, A.
AU - Ofori, M. F.
AU - Akanmori, B. D.
AU - Shuaibu, M. N.
AU - Kikuchi, M.
AU - Hirayama, K.
PY - 2012/8
Y1 - 2012/8
N2 - Fc gamma receptor (FcγR) provides an important link between humoral and cellular immune responses. FcγRIIa-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 (FcγRIIa-H131R) and rs150311303 (FcγRIIa-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 FcγRIIa haplotype variants. The binding assay revealed the rs150311303, which was observed only among carriers of the FcγRIIa-131RR genotype for the rs1801274 to consistently enhance binding capacities to all IgG subclasses. Thus, of the three FcγRIIa haplotype variants observed in this study population, the FcγRIIa RL haplotype variant was observed to have the highest binding ability to IgG1, IgG3 and IgG4.
AB - Fc gamma receptor (FcγR) provides an important link between humoral and cellular immune responses. FcγRIIa-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 (FcγRIIa-H131R) and rs150311303 (FcγRIIa-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 FcγRIIa haplotype variants. The binding assay revealed the rs150311303, which was observed only among carriers of the FcγRIIa-131RR genotype for the rs1801274 to consistently enhance binding capacities to all IgG subclasses. Thus, of the three FcγRIIa haplotype variants observed in this study population, the FcγRIIa RL haplotype variant was observed to have the highest binding ability to IgG1, IgG3 and IgG4.
UR - http://www.scopus.com/inward/record.url?scp=84864299233&partnerID=8YFLogxK
U2 - 10.1111/j.1365-3083.2012.02715.x
DO - 10.1111/j.1365-3083.2012.02715.x
M3 - Article
C2 - 22540264
AN - SCOPUS:84864299233
SN - 0300-9475
VL - 76
SP - 167
EP - 174
JO - Scandinavian Journal of Immunology
JF - Scandinavian Journal of Immunology
IS - 2
ER -