Differences in Fcgamma receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali

Background: The Ig Fc receptor family is an important link between the humoral and cellular immune systems. The association of a dimorphism in amino acid 131 (R/H) of the Fc gamma RIIa with malaria severity, the R-allele being associated with a milder disease outcome, led to the investigation of the possible impact of this polymorphism in the interethnic difference in malaria susceptibility seen between the Fulani and Dogon in Mali. Methods: Plasma from individuals from Mali (164 Fulani and 164 Dogon) were analysed for malaria-reactive and total IgG subclass antibodies using ELISA, and the same individuals were also genotyped for the Fc gamma RIIa R131H polymorphism using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by unpaired t-test and ANOVA, and genotype differences were tested by chi(2)-test. Results: While the two ethnic groups showed a similar frequency of the Fc gamma RIIa 131 R/ H heterozygote genotype, 131R/ R dominated over the 131 H/ H genotype in the Dogon whereas the Fulani presented a similar frequency of the two homozygote genotypes. The two alleles were evenly distributed in the Fulani, while the Dogon were clearly biased towards the R-allele. The Fulani showed higher levels of anti-malarial IgG1,-2 and-3 antibodies, with a higher proportion of IgG2, than the Dogon. In the Fulani, H-allele carriers had higher anti-malarial IgG2 levels than R/ R homozygotes, while in the Dogon, the R-allele carriers showed the higher IgG2 levels. For antimalarial IgG3, the R-allele carriers in the Fulani had higher levels than the H/ H homozygotes. Conclusion: Taken together, the results showed marked interethnic differences in Fc gamma RIIa R131H genotypes. Furthermore, the results indicate that the Fc.RIIa R131H genotype may influence the IgG subclass responses related to protection against malaria, and that IgG2 may be of importance in this context.