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- Giha, Hayder A., et al.
(author)
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Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.
- 2009
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.
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| 2. |
- Israelsson, Elisabeth, et al.
(author)
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Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa
- 2009
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In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:136
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Journal article (peer-reviewed)abstract
- Background C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group. Methods The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes. Results The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T. Conclusion This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.
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| 3. |
- Nasr, Amre, et al.
(author)
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FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan
- 2009
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In: Malaria Journal. - : BioMed Central Ltd.. - 1475-2875. ; 8:43, s. 1-10
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Journal article (peer-reviewed)abstract
- BACKGROUND: A SNP at position 131, in the FcgammaRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcgammaRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria. METHODS: Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcgammaRIIa-131 polymorphism. For comparison, 101 non-Fulani donors - (Masaleit, Hausa and Four) - living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses) to four malaria antigens (AMA-1, MSP 2 - 3D7 & FC27, Pf332-C231) were measured using indirect enzyme-linked immunosorbent assays. RESULTS: The FcgammaRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61-5.97, P value < 0.001). The Fulani showed lower anti-malarial IgG1 and IgG3 antibody levels as compared to the non-Fulani and higher levels of IgG2 antibodies. CONCLUSION: The FcgammaRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.
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