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Human Candidate Polymorphisms in Sympatric Ethnic Groups Differing in Malaria Susceptibility in Mali
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Science, Technique and Technologies of Bamako (USTTB), Mali.
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, e75675Article in journal (Refereed) Published
Abstract [en]

Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10(-15)). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.

Place, publisher, year, edition, pages
2013. Vol. 8, no 10, e75675
Keyword [en]
Malaria, Malarial parasites, Ethnic epidemiology, Spleen, Variant genotypes, Mali, Parasitic diseases, Genetic polymorphism
National Category
Biological Sciences Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-96099DOI: 10.1371/journal.pone.0075675ISI: 000325434500036OAI: oai:DiVA.org:su-96099DiVA: diva2:664181
Note

AuthorCount:15;

Funding agencies:

Wellcome Trust WT077383/Z/05/Z, 090770/Z/09/Z, 075491/Z/04, 090532/Z/09/Z, 098051;  Foundation of the National Institutes of Health, Bill & Melinda Gates' Grand Challenges in Global Health Initiative 566; Medical Research Council G0600718, G0600230; Fundacao para Ciencia e Tecnologia, Portugal Pest-OE/MAT/UI0006/2011 

Available from: 2013-11-14 Created: 2013-11-11 Last updated: 2017-12-06Bibliographically 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.
Keyword
Malaria, Fulani, Dogon, Blood group, SNPs, IL-4, FcγRIIa, antibody level
National Category
Other Medical Sciences
Research subject
Molecular Bioscience
Identifiers
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)
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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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