Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa

Israelsson Elisabeth, Ekström Mattias, Nasr Amre, Dolo Amagana, Kearsley Susannah, Arambepola Gishanthi, Homann Manijeh, Maiga Bakary, Doumbo, Elghazali Gehad, Giha, Troye-Blomberg Marita, Berzins Klavs, Tornvall Per

Description

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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2009
• Nombre de lectures: 9
• Langue: English

Extrait

Malaria Journal

BioMedCentral

Open Access Research Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa 1 21 3 Elisabeth Israelsson, Mattias Ekström, Amre Nasr, Amagana Dolo, 1 1 1 Susannah Kearsley, Gishanthi Arambepola, Manijeh Vafa Homann, 3 34,5 6,7 Bakary Maiga, Ogobara K Doumbo, Gehad ElGhazali, Hayder A Giha, 1 12 Marita TroyeBlomberg, Klavs Berzinsand Per Tornvall*

1 2 Address: Departmentof Immunology, WennerGren Institute, Stockholm University, Stockholm, Sweden,Department of Cardiology, Karolinska 3 University Hospital Solna, 17176 Stockholm, Sweden,Malaria Research and Training Center (MRTC), Faculty of Medicine and Pharmacy, 4 University of Bamako, Bamako, Mali,Department of Immunology, Faculty of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia, 5 6 Department of Microbiology and Immunology, Faculty of Medicine, University of Khartoum, Sudan, MalariaResearch Center, Department of 7 Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan andDepartment of Medical Biochemistry, College of Medicine and Health Sciences, Arabian Gulf University, Manama, Bahrain

Email: Elisabeth Israelsson  [e-mail]; Mattias Ekström  [e-mail]; Amre Nasr  [e-mail]; Amagana Dolo  [e-mail]; Susannah Kearsley  [e-mail]; Gishanthi Arambepola  [e-mail]; Manijeh Vafa Homann  [e-mail]; Bakary Maiga  [e-mail]; Ogobara K Doumbo  [e-mail]; Gehad ElGhazali  [e-mail]; Hayder A Giha  [e-mail]; Marita TroyeBlomberg  [e-mail]; Klavs Berzins  [e-mail]; Per Tornvall*  [e-mail] * Corresponding author

Published: 22 June 2009Received: 15 April 2009 Accepted: 22 June 2009 Malaria Journal2009,8:136 doi:10.1186/147528758136 This article is available from: http://www.malariajournal.com/content/8/1/136 © 2009 Israelsson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Creactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcgreceptors. 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 theCRPgene 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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