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Host genetic factors in malaria

Human populations in malaria-endemic regions exhibit a variety of genetic polymorphisms which are absent or rare in malaria-free areas. The correlation between these genetic dispositions and the endemicity of malaria suggests a protective effect of the former against the latter, and consequently, positive selection during evolution.

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Susceptibilty and host resistance

It is estimated that each 25%-30% in the variability in the incidence of malaria can be attributed to genetic and environmental factors, respectively. In various study designs on the different types of manifestation of Plasmodium falciparum infection, associations between genetic polymorphisms and malaria are examined. The selection of polymorphisms under study follows hypotheses on the role of e.g. immune receptors in the pathophysiology of malaria. Beyond epidemiological aspects of influencing the risks of infection, disease, and fatality, functional analyses are increasingly focused on. These examinations aim at an improved understanding of the epidemiological and functional relationships between protective or disposing factors and disease to ultimately generate starting-points for therapeutical or preventive measures.

Project Details

Principal Investigator: Prof. Dr. med. Frank P. Mockenhaupt

Co-workers: Steffen Zander, Stefanie Meese, Prabhanjan Gai, doctoral studentsSteffen Zander

Co-operations: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
University of Rwanda, Butare, Rwanda
Centre for Cellular and Molecular Biology, Hyderbad, Indien
Karnataka Institute for DNA Research, Dharwad-Hubli, Indien
Australian National University, Canberra, Australien
Institut für Mikrobiologie und Hygiene, Charité, Berlin

Project duration: Since 1998, ongoing

Project status: Laboratory examinations, analysis, planning

Funding: Charité, DFG, GRK 1673, GRK 2290, Sonnenfeld-FoundationCharité, Industry, Sonnenfeld Foundation


Apoorv TS, Babu PP, Meese S, Gai PP, Bedu-Addo G, Mockenhaupt FP. Matrix metalloproteinase-9 polymorphism 1562 C > T (rs3918242) associated with protection against placental malaria. Am J Trop Med Hyg. 2015 Jul;93(1):186-8.

Bedu-Addo G, Gai PP, Meese S, Eggelte TA, Thangaraj K, Mockenhaupt FP. Reduced prevalence of placental malaria in primiparae with blood group O. Malar J. 2014 Jul 28;13:289.

Gai PP, Meese S, Bedu-Addo G, Gahutu JB, Mockenhaupt FP. No association of the p53 codon 72 polymorphism with malaria in Ghanaian primiparae and Rwandan children. Am J Trop Med Hyg. 2014 Jun;90(6):1133-4.

Danquah I, Gahutu JB, Zeile I, Musemakweri A, Mockenhaupt FP. Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children. Trop Med Int Health. 2014 Jan;19(1):117-22.

Bedu-Addo G, Meese S, Mockenhaupt FP. An ATP2B4 polymorphism protects against malaria in pregnancy. J Infect Dis. 2013 May 15;207(10):1600-3.

Holmberg V, Onkamo P, Lahtela E, Lahermo P, Bedu-Addo G, Mockenhaupt FP, Meri S. Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria. Malar J. 2012 Mar 2;11:61.

Gahutu JB, Musemakweri A, Harms G, Mockenhaupt FP. Prevalence of classic erythrocyte polymorphisms among 749 children in southern highland Rwanda. Trans R Soc Trop Med Hyg. 2012 Jan;106(1):63-5.

Danquah I, Ziniel P, Eggelte TA, Ehrhardt S, Mockenhaupt FP. Influence of haemoglobins S and C on predominantly asymptomatic Plasmodium infections in northern Ghana. Trans R Soc Trop Med Hyg. 2010 2010 Nov;104(11):713-9.

Hamann L, Bedu-Addo G, Eggelte TA, Schumann RR, Mockenhaupt FP. The toll-like receptor 1 variant S248N influences placental malaria. Infect Genet Evol. 2010 Aug;10(6):785-9.

McCall MB, Ferwerda B, Hopman J, Ploemen I, Maiga B, Daou M, Dolo A, Hermsen CC, Doumbo OK, Bedu-Addo G, van der Meer JW, Troye-Blomberg M, van der Ven AJ, Schumann RR, Sauerwein RW, Mockenhaupt FP, Netea MG. Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations. Eur Cytokine Netw. 2010 Jun;21(2):77-83.

Hamann L, Kumpf O, Schuring RP, Alpsoy E, Bedu-Addo G, Bienzle U, Oskam L, Mockenhaupt FP, Schumann RR. Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy. BMC Med Genet. 2009 Jul 14;10:65.

Ferwerda B, Alonso S, Banahan K, McCall MB, Giamarellos-Bourboulis EJ, Ramakers BP, Mouktaroudi M, Fain PR, Izagirre N, Syafruddin D, Cristea T, Mockenhaupt FP, Troye-Blomberg M, Kumpf O, Maiga B, Dolo A, Doumbo O, Sundaresan S, Bedu-Addo G, van Crevel R, Hamann L, Oh DY, Schumann RR, Joosten LA, de la Rúa C, Sauerwein R, Drenth JP, Kullberg BJ, van der Ven AJ, Hill AV, Pickkers P, van der Meer JW, O'Neill LA, Netea MG. Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10272-7.

Danquah I, Mockenhaupt FP. Alpha(+)-thalassaemia and malarial anaemia. Trends Parasitol. 2008 Nov;24(11):479-81.

Veenemans J, Andang'o PE, Mbugi EV, Kraaijenhagen RJ, Mwaniki DL, Mockenhaupt FP, Roewer S, Olomi RM, Shao JF, van der Meer JW, Savelkoul HF, Verhoef H. Alpha+-thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya. J Infect Dis. 2008 Aug 1;198(3):401-8.

Holmberg V, Schuster F, Dietz E, Sagarriga Visconti JC, Anemana SD, Bienzle U, Mockenhaupt FP. Mannose-binding lectin variant associated with severe malaria in young African children. Microbes Infect. 2008 Apr;10(4):342-8.

Weise A, Lambertz U, Thomé N, Bartz U, Krefft M, Mockenhaupt F, Bienzle U, Schöndorf T, Forst T, Pfützner A. A fast and reliable single-run method for genotyping of the human cytochrome P450 2C8 gene for different ethnic groups. Clin Lab. 2006;52(11-12):599-603.

Mockenhaupt FP, Hamann L, von Gaertner C, Bedu-Addo G, von Kleinsorgen C, Schumann RR, Bienzle U. Common polymorphisms of toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy. J Infect Dis. 2006 Jul 15;194(2):184-8.

Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh NR, Otchwemah RN, Dietz E, Ehrhardt S, Schroder NW, Bienzle U, Schumann RR. Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):177-82.

Röwer S, Bienzle U, Weise A, Lambertz U, Forst T, Otchwemah RN, Pfützner A, Mockenhaupt FP. Short communication: high prevalence of the cytochrome P450 2C8*2 mutation in Northern Ghana. Trop Med Int Health. 2005 Dec;10(12):1271-3.

Meissner PE, Coulibaly B, Mandi G, Mansmann U, Witte S, Schiek W, Müller O, Schirmer RH, Mockenhaupt FP, Bienzle U. Diagnosis of red cell G6PD deficiency in rural Burkina Faso: comparison of a rapid fluorescent enzyme test on filter paper with polymerase chain reaction based genotyping. Br J Haematol. 2005 Nov;131(3):395-9.

Cramer JP, Nüssler AK, Ehrhardt S, Burkhardt J, Otchwemah RN, Zanger P, Dietz E, Gellert S, Bienzle U, Mockenhaupt FP. Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria. Trop Med Int Health. 2005 Jul;10(7):672-80.

Bienzle U, Eggelte TA, Adjei LA, Dietz E, Ehrhardt S, Cramer JP, Otchwemah RN, Mockenhaupt FP. Limited influence of haptoglobin genotypes on severe malaria in Ghanaian children. Trop Med Int Health. 2005 Jul;10(7):668-71.

Cramer JP, Mockenhaupt FP, Ehrhardt S, Burkhardt J, Otchwemah RN, Dietz E, Gellert S, Bienzle U. iNOS promoter variants and severe malaria in Ghanaian children. Trop Med Int Health. 2004 Oct;9(10):1074-80.

Mockenhaupt FP, Ehrhardt S, Cramer JP, Otchwemah RN, Anemana SD, Goltz K, Mylius F, Dietz E, Eggelte TA, Bienzle U. Hemoglobin C and resistance to severe malaria in Ghanaian children. J Infect Dis. 2004 Sep 1;190(5):1006-9.

Mockenhaupt FP, Ehrhardt S, Gellert S, Otchwemah RN, Dietz E, Anemana SD, Bienzle U. Alpha(+)-thalassemia protects African children from severe malaria. Blood. 2004 Oct 1;104(7):2003-6.

Mockenhaupt FP, Ehrhardt S, Otchwemah R, Eggelte TA, Anemana SD, Stark K, Bienzle U, Kohne E. Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria. Trans R Soc Trop Med Hyg. 2004 May;98(5):302-10.

Mockenhaupt FP, Mandelkow J, Till H, Ehrhardt S, Eggelte TA, Bienzle U. Reduced prevalence of Plasmodium falciparum infection and of concomitant anaemia in pregnant women with heterozygous G6PD deficiency. Trop Med Int Health. 2003 Feb;8(2):118-24.

Mockenhaupt FP, Rong B, Till H, Thompson WN, Bienzle U. Short report: increased susceptibility to Plasmodium malariae in pregnant alpha(+)-thalassemic women. Am J Trop Med Hyg. 2001 Jan-Feb;64(1-2):6-8.

Mockenhaupt FP, May J, Bergqvist Y, Meyer CG, Falusi AG, Bienzle U. Evidence for a reduced effect of chloroquine against Plasmodium falciparum in alpha-thalassaemic children. Trop Med Int Health. 2001 Feb;6(2):102-7.

Mockenhaupt FP, Rong B, Gunther M, Beck S, Till H, Kohne E, Thompson WN, Bienzle U. Anaemia in pregnant Ghanaian women: importance of malaria, iron deficiency, and haemoglobinopathies. Trans R Soc Trop Med Hyg. 2000 Sep-Oct;94(5):477-83.

Mockenhaupt FP, Bienzle U, May J, Falusi AG, Ademowo OG, Olumese PE, Meyer CG. Plasmodium falciparum infection: influence on hemoglobin levels in alpha-thalassemia and microcytosis. J Infect Dis. 1999 Sep;180(3):925-8.

Mockenhaupt FP, Falusi AG, May J, Ademowo OG, Olumese PE, Meyer CG, Bienzle U. The contribution of alpha+-thalassaemia to anaemia in a Nigerian population exposed to intense malaria transmission. Trop Med Int Health. 1999 Apr;4(4):302-7.