Omar A H, Shibata H, Yasunami M, Yamazaki A, Ofori M F, Akanmori B D, Shuaibu M N, Kikuchi M, Hirayama K
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, Nagasaki, Japan.
Scand J Immunol. 2012 Aug;76(2):167-74. doi: 10.1111/j.1365-3083.2012.02715.x.
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.
Fcγ受体（FcγR）在体液免疫和细胞免疫反应之间提供了重要联系。FcγRIIa-H131R多态性与不同人群中IgG亚类的差异结合以及疟疾流行地区严重疟疾表型的易感性有关。在本研究中，调查了FCGR2A基因多态性对加纳队列儿童有症状疟疾易感性的影响。通过直接DNA测序对429名健康加纳儿童的血样进行FCGR2A多态性基因分型。计算多态性变体对有症状疟疾的归因风险和相对风险。在研究人群中鉴定出两种主要的FCGR2A多态性，即rs1801274A/G（FcγRIIa-H131R）和rs150311303（FcγRIIa-ins170L），对其风险评估未显示与有症状疟疾易感性有显著关联。还通过对转染了FcγRIIa单倍型变体的HEK细胞进行流式细胞术分析来评估这些多态性对IgG亚类的结合能力，以此检验这些多态性的功能意义。结合试验显示，rs150311303仅在rs1801274的FcγRIIa-131RR基因型携带者中观察到，它能持续增强对所有IgG亚类的结合能力。因此，在本研究人群中观察到的三种FcγRIIa单倍型变体中，FcγRIIa(RL)单倍型变体对IgG1、IgG3和IgG4的结合能力最高。
