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Fc gamma Receptor IIa-H131R Polymorphism and Malaria Susceptibility in Sympatric Ethnic Groups, Fulani and Dogon of Mali
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases/Faculty of Medicine, Pharmacy and Odonto, Stomatology, Bamako, Mali.
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2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 1, 43-50 p.Article in journal (Refereed) Published
Abstract [en]

It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.

Place, publisher, year, edition, pages
2014. Vol. 79, no 1, 43-50 p.
National Category
URN: urn:nbn:se:su:diva-99654DOI: 10.1111/sji.12122ISI: 000328598900006PubMedID: 24117665OAI: diva2:687835

Funding agencies:

Malaria-GEN Project; Medical Research Council; Wellcome Trust;  Fundacao para Ciencia e Tecnologia, Portugal, Pest-OE/MAT/UI0006/2011 

Available from: 2014-01-15 Created: 2014-01-15 Last updated: 2014-01-20Bibliographically approved
In thesis
1. Human candidate polymorphisms and malaria susceptibility in sympatric ethnic groups, The Fulani and The Dogon of Mali
Open this publication in new window or tab >>Human candidate polymorphisms and malaria susceptibility in sympatric ethnic groups, The Fulani and The Dogon of Mali
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In malaria endemic regions, resistance to malaria constitutes a critical selective pressureon genetic polymorphisms that regulate immune defense and inflammatory pathways.Differences in malaria susceptibility between sympatric ethnic groups have been described inMali. The Fulani are less susceptible to malaria compared to the neighboring group the Dogon,in spite of similar socio-economic and environmental conditions.

Paper I is focused on IL-4-590 T/C polymorphism and correlation with levels of malariaspecific IgG, IgG (1-4) subclasses as well as malaria specific and total IgE level in the two ethnicgroups. Our data show that the Fulani individual carrying the IL-4-590 T allele found to havehigher parasite carriage rate and had higher levels of malaria-specific IgG4 and IgE compared tothe individual carrying the C allele. No such differences were seen within the Dogon.Paper II investigated 166 SNPs in the human host in individuals belonging to the Fulani and theDogon ethnic groups. These SNPs were correlated with total IgG against AMA-1, MSP-1, MSP-2 and CSP antigens as well as total IgE level. All antibody levels were higher in the Fulanicompared to the Dogon and strengthens previous finding that antibodies might play a role in theprotection seen in the Fulani. We identified higher frequencies of the protective blood group O.Several allelic differences between the two ethnic groups were found in CD36, IL-4, RTN3 andADCY9. Moreover several polymorphisms in SLC22A4, IRF1, IL5, LTA and TNF have beenfound to be correlated with anti-MSP antibody level; TLR6, IL3, TNF, and IL22 found to becorrelated with anti-MSP-2 antibody level in the Fulani. Such association was not seen in theDogon.

In Paper III, the same individuals, as in paper II, were investigated with a focus on the FcγRIIapolymorphism and correlation with levels of anti-AMA-1, MSP-1, MSP-2, CSP specificantibodies as well as total IgE level. The genotype distribution and allele frequency weresignificantly different between the Fulani and the Dogon with the Fulani being HH, H allele- andthe Dogon RR, R allele carriers. A correlation between the HH genotype and the H allele andprotection against mild malaria was seen in the Fulani but not in the DogonTaken together our study has found significant genetic differences between the Fulani and theDogon Ethnic groups, which suggest that ethnicity should be taken into account in monitoring ofimmunological studies and vaccines trials in malaria endemic areas.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 90 p.
Malaria, Fulani, Dogon, Blood group, SNPs, IL-4, FcγRIIa, antibody level
National Category
Other Medical Sciences
Research subject
Molecular Bioscience
urn:nbn:se:su:diva-99613 (URN)978-91-7447-845-7 (ISBN)
Public defence
2014-02-21, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 13:00 (English)
Available from: 2014-01-30 Created: 2014-01-14 Last updated: 2015-02-24Bibliographically approved

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Maiga, BakaryTroye Blomberg, Marita
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