Studies on the Distribution of the Allotypic Variants of the IgG Receptors (FcyRIIa and FcyRIIIb) and their Association with severe Clinical Malaria among Ghanaian Children

Abstract

The immunoglobulin G (IgG) receptors FcyRIIa and FcyRIIIb vary among different ethnic groups, and more importantly, are also known to be associated with either susceptibility to or protection from certain diseases. These variations are manifest as differences in the antigen-binding capabilities of the receptors. The genes encoding for these receptors are polymorphic and these also vary among populations. These variations can be investigated using molecular methods such as PCR. The aim of the present study was to determine if there were any significant differences in the distribution of these genotypes among some of the ethnic groups in Ghana and also if there was any association between the genotypes and the incidence of severe malaria. A total number of 329 children, belonging to four different tribes were recruited for the study, of which 75 healthy individuals formed the control group. The 254 patients who were recruited were diagnosed as having uncomplicated, severe anaemia or cerebral malaria. Human DNA was isolated from filter paper blood blots for PCR analysis using allele-specific primers for FcyRIIa to detect H/H131, H/R131, R/R131, and FcyRIIIb to detect NA1/NA1 and NA2/NA2 genotypes. The results obtained revealed that there was no association between ethnicity and the FcyRIIa genotype, (P=0.78) and FcyRIIIb genotypes (P=0.23). W ith regard to the incidence of malaria and the FcyRIIa genotypes, the following associations were found (P<0.002 in all cases); firstly, there were significantly more of the homozygous FcyRIIa-R/R131 genotypes among patients with severe anaemia and cerebral malaria. Secondly, there were significantly less of the homozygous H/H131 in all the three forms of malaria and thirdly, the heterozygous FcyRHa-H/R131 was associated with only severe anaemia. These observations suggest that the homozygosity of the R allele is a heritable risk factor for severe malaria, while the H allele confers some degree of protection against the disease both in the homozygous and heterozygous state. Similarly, no association was found between the FcyRIIIb and ethnicity (P>0.05. The homozygous NA1/NA1 was found to be significantly dominant among the patient group (P=0.003). The NA2/NA2 genotype on the other hand was significantly reduced in the patient group (P=0.000), and also in all the three forms of the diseases (P< 0.04). The heterozygous NA1/NA2 was found to be intermediate between the two, but was significantly underepresented in the cerebral and severe anaemia patients (P< 0.001). The null genotype was found to be overrepresented within the patient group (P=0.02). These findings suggest that the NA2 offers protection against all forms of malaria and this effect is even observed in the heterozygotes NA1/NA2 among the severe anaemia and cerebral malaria groups. NA1, on the other hand is a heritable predisposing factor to symptomatic malaria.