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Single nucleotide polymorphisms related to immune responses in Plasmodium falciparum malaria
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
Responsible organisation
2008 (English)Doctoral thesis, monograph (Other academic)
Abstract [en]

The current research is directed towards dissection of host genetic factors involved in host immune response and the malaria disease outcome. A possible association between FcγRIIa polymorphism and anti-malarial antibody (A.M.A) responses were investigated in Sudanese patients in relation to clinical outcome of falciparum malaria. The frequency of the R/R131 genotype was significantly higher in patients with severe malaria as compared with mild malaria. A.M.A IgG3 was shown to be associated with reduced risk of clinical malaria in individuals carrying the H/H131 genotype. Low levels of IgG2 reactive with the Pf332-C231 antigen were associated with lower risk of severe malaria in individuals carrying the H131 allele.

Fulani and Masaleit, two sympatric ethnic groups in Sudan, are characterized by marked differences in susceptibility to falciparum malaria. We investigated whether the two populations differ in the frequency of GM/KM allotypes. The distribution of GM/KM phenotypes differed significantly among the two groups, with Gm 6 being significantly lower among the Fulani, and the combined frequency of Km 1,3 and Gm 1,17 5,6,13,14 phenotypes was found to be higher among Masaleit.

In interethnic study we investigated whether the two groups differ in the frequency of FcγRIIa and HbAS genotypes. The frequency of the H/H131, R/R13 and HbAS genotypes differed significantly among the two groups. Moreover, the Fulani showed higher levels of A.M.A IgG2 and lower IgG1 and IgG3 when compared to their sympatric non-Fulani neighbours.

A tri-allelic SNP (C/T/A) in the CRP gene was investigated for possible ethnic associations. The A allele, which is associated with higher basal CRP levels, was found to be less frequent in the Fulani compared with non-Fulani ethnic groups both in Sudan and Mali.

In conclusion, our results suggest possible associations between FcγRIIa, CRP genotypes, GM/KM allotypes, and anti-malarial antibody responses and the clinical outcome of falciparum malaria.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2008. , 60 p.
Keyword [en]
FcγRIIa-R/H131, CRP genotypes, GM/KM allotypes, IgG, and malaria, Sudan
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-8168ISBN: 978-91-7155-726-1 (print)OAI: oai:DiVA.org:su-8168DiVA: diva2:199738
Public defence
2008-10-10, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-09-18 Created: 2008-09-11Bibliographically approved
List of papers
1. Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood-stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
Open this publication in new window or tab >>Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood-stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
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2007 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, Vol. 66, no 1, 87-96 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25447 (URN)10.1111/j.1365-3083.2007.01947.x (DOI)000247478000011 ()
Available from: 2008-09-18 Created: 2008-09-11 Last updated: 2009-05-08Bibliographically approved
2. Significant differences in GM allotype frequencies between two sympatric tribes with markedly differential susceptibility to malaria
Open this publication in new window or tab >>Significant differences in GM allotype frequencies between two sympatric tribes with markedly differential susceptibility to malaria
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2007 In: Parasite immunology, ISSN http://, Vol. 29, no 5, 267-269 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25448 (URN)
Note
Part of urn:nbn:se:su:diva-8168Available from: 2008-09-18 Created: 2008-09-11Bibliographically approved
3. Interethnic differences in carriage of haemoglobin AS and Fcγ receptor IIa (CD32) genotypes in children living in eastern Sudan
Open this publication in new window or tab >>Interethnic differences in carriage of haemoglobin AS and Fcγ receptor IIa (CD32) genotypes in children living in eastern Sudan
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2008 In: Acta Tropica, ISSN 0001-706X, Vol. 105, no 2, 191-195 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25449 (URN)000253323300014 ()
Note
Part of urn:nbn:se:su:diva-8168Available from: 2008-09-18 Created: 2008-09-11Bibliographically approved
4.
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5. Polymorphism in the CRP gene may contribute to the lower susceptibility to malaria of the Fulani ethnic group in Africa
Open this publication in new window or tab >>Polymorphism in the CRP gene may contribute to the lower susceptibility to malaria of the Fulani ethnic group in Africa
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25451 (URN)
Note
Part of urn:nbn:se:su:diva-8168Available from: 2008-09-18 Created: 2008-09-11 Last updated: 2010-01-13Bibliographically approved

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