Chapter 24 : Host Genetic Factors in Resistance and Susceptibility to Malaria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Host Genetic Factors in Resistance and Susceptibility to Malaria, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817558/9781555813307_Chap24-1.gif /docserver/preview/fulltext/10.1128/9781555817558/9781555813307_Chap24-2.gif


Well-controlled genetic studies are easier to conduct with mice than with humans, and it has long been known that certain strains of mice consistently show a greater degree of resistance to infection than other strains. It is clear that these differences are primarily genetic, rather than environmental or acquired. This chapter discusses specific genetic loci that have been identified as responsible for some of these differences. Genetic factors also appear to underlie some striking differences in resistance to malaria that have been observed between ethnic groups who live in the same area. The chapter deals with the growing list of genes that show some evidence of influencing resistance to malaria. Glycophorins A and B, encoded by the homologous genes GYPA and GYPB, are major sialoglycoproteins of the erythrocyte membrane, which carries the antigenic determinants for various blood groups. Hemoglobin S (HbS) homozygotes have sickle cell disease, a debilitating and often fatal disorder caused by the red blood cell deformities that result from this structural defect, particularly at low oxygen concentrations. The thalassemias are a group of genetic disorders due to defective production of α- or β- globin chains, arising from a diverse set of deletions and other disruptions of the globin gene clusters on chromosomes 11 and 16. Haptoglobin, encoded by the HP gene, is a protein found in plasma. Parasite sequestration in cerebral capillaries, a hallmark of human cerebral malaria, is notable by its absence in the ANKA (PBA) experimental model.

Citation: Kwiatkowski D, Luoni G. 2005. Host Genetic Factors in Resistance and Susceptibility to Malaria, p 462-479. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch24

Key Concept Ranking

Major Histocompatibility Complex
Tumor Necrosis Factor
Nitric Oxide Synthase
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


1. Abraham, L. J.,, and K. M. Kroeger. 1999. Impact of the −308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J. Leukoc. Biol. 66:562566.
2. Ackerman, H. C.,, G. Ribas,, M. Jallow,, R. Mott,, M. Neville,, F. Sisay-Joof,, M. Pinder,, R. D. Campbell,, and D. P. Kwiatkowski. 2003. Complex haplotypic structure of the central MHC region flanking TNF in a West African population. Genes Immun. 4:476486.
3. Agarwal, A.,, A. Guindo,, Y. Cissoko,, J. G. Taylor,, D. Coulibaly,, A. Kone,, K. Kayentao,, A. Djimde,, C. V. Plowe,, O. Doumbo,, T. E. Wellems,, and D. Diallo. 2000. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96:23582363.
4. Aidoo, M.,, P. D. McElroy,, M. S. Kolczak,, D. J. Terlouw,, F. O. ter Kuile,, B. Nahlen,, A. A. Lal,, and V. Udhayakumar. 2001.Tumor necrosis factor- alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX. Genet. Epidemiol. 21:201211.
5. Aitman, T. J.,, L.D. Cooper,, P. J. Norsworthy,, F.N. Wahid,, J. K. Gray,, B.R. Curtis,, P. M. McKeigue,, D. Kwiatkowski,, B. M. Greenwood,, R.W. Snow,, A.V. Hill,, and J. Scott. 2000. Malaria susceptibility and CD36 mutation. Nature 405:10151016.
6. Allen, S. J.,, S. Bennett,, E. M. Riley,, P. A. Rowe,, P. H. Jakobsen,, A. O’Donnell,, and B. M. Greenwood. 1992. Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia. Trans. R. Soc.Trop. Med. Hyg. 86:494498.
7. Allen, S. J.,, A. O’Donnell,, N. D. Alexander,, M. P. Alpers,, T. E. A. Peto,, J. B. Clegg,, and D. J. Weatherall. 1997.a1-Thalassemia protects children against disease caused by other infections as well as malaria. Proc. Natl.Acad. Sci.USA 94:1473614741.
8. Allen, S. J.,, A. O’Donnell,, N. D. Alexander,, C. S. Mgone,, T. E. Peto,, J. B. Clegg,, M. P. Alpers,, and D. J. Weatherall. 1999. Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3.Am.J.Trop. Med. Hyg. 60:10561060.
9. Allison, A. C. 1954. Protection afforded by sickle-cell trait against subtertian malareal infection. Br. Med. J. 4857:290294.
10. Amani, V.,, M. I. Boubou,, S. Pied,, M. Marussig,, D. Walliker,, D. Mazier,, and L. Renia. 1998. Cloned lines of Plasmodium berghei ANKA differ in their abilities to induce experimental cerebral malaria. Infect. Immun. 66:40934099.
11. Aucan, C.,, A. J. Walley,, B. M. Greenwood,, and A.V. Hill. 2002. Haptoglobin genotypes are not as- sociated with resistance to severe malaria in The Gambia. Trans. R. Soc.Trop. Med. Hyg. 96:327328.
12. Aucan, C.,, A. J. Walley,, B. J. Hennig,, J. Fitness,, A. Frodsham,, L. Zhang,, D. Kwiatkowski,, and A.V. Hill. 2003. Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in The Gambia. Genes Immun. 4:275282.
13. Bagot, S.,, S. Campino,, C. Penha-Goncalves,, S. Pied,, P. A. Cazenave,, and D. Holmberg. 2002a. Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proc. Natl.Acad. Sci. USA 99:99199923.
Bagot, S.,, M. Idrissa Boubou,, S. Campino,, C. Behrschmidt,, O. Gorgette,, J. L. Guenet,, C. Penha-Goncalves,, D. Mazier,, S. Pied,, and P.A. Cazenave. 2002.b. Susceptibility to experimental cerebral malaria induced by Plasmodium berghei ANKA in inbred mouse strains recently derived from wild stock. Infect. Immun. 70:20492056.
15. Baird, J. K. 1995. Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. Parasitol.Today 11:105111.
16. Baird, J. K.,, S. Masbar,, H. Basri,, S. Tirtokusumo,, B. Subianto,, and S. L. Hoffman. 1998. Agedependent susceptibility to severe disease with primary exposure to Plasmodium falciparum. J. Infect. Dis. 178:592595.
17. Barnwell, J.W.,, A. S. Asch,, R. L. Nachman,, M. Yamaya,, M. Aikawa,, and P. Ingravallo. 1989. A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J. Clin. Investig. 84:765772.
18. Baum, J.,, R. H. Ward,, and D. J. Conway. 2002. Natural selection on the erythrocyte surface. Mol. Biol. Evol. 19:223229.
19. Bayley, J. P.,, T. H. Ottenhoff,, and C. L. Verweij. 2004. Is there a future for TNF promoter polymorphisms? Genes Immun. 5:315329.
20. Bellamy, R.,, D. Kwiatkowski,, and A.V. Hill. 1998a. Absence of an association between intercellular adhesion molecule 1, complement receptor 1 and interleukin 1 receptor antagonist gene polymorphisms and severe malaria in a West African population. Trans. R. Soc.Trop. Med. Hyg. 92:312316.
21. Bellamy, R.,, C. Ruwende,, K. P. McAdam,, M. Thursz,, M. Sumiya,, J. Summerfield,, S. C. Gilbert,, T. Corrah,, D. Kwiatkowski,, H.C. Whittle,, and A.V. Hill. 1998b. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. QJM 91:1318.
22. Bennett, S.,, S. J. Allen,, O. Olerup,, D. J. Jackson,, J. G. Wheeler,, P.A. Rowe,, E. M. Riley,, and B. M. Greenwood. 1993. Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community. Trans. R. Soc.Trop. Med. Hyg. 87:286287.
23. Berendt, A. R.,, D. L. Simmons,, J. Tansey,, C. I. Newbold,, and K. Marsh. 1989. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341:5759.
24. Burgner, D.,, S. Usen,, K. Rockett,, M. Jallow,, H. Ackerman,, A. Cervino,, M. Pinder,, and D. P. Kwiatkowski. 2003. Nucleotide and haplotypic diversity of the NOS2A promoter region and its relationship to cerebral malaria.Hum.Genet. 112: 379386.
25. Burgner, D.,, W. Xu,, K. Rockett,, M. Gravenor,, I. G. Charles,, A.V. Hill,, and D. Kwiatkowski. 1998. Inducible nitric oxide synthase polymorphism and fatal cerebral malaria. Lancet 352:11931194.
26. Burt, R. A.,, T. M. Baldwin,, V. M. Marshall,, and S. J. Foote. 1999.Temporal expression of an H2- linked locus in host response to mouse malaria. Immunogenetics 50:278285.
27. Burt, R. A.,, V. M. Marshall,, J. Wagglen,, F. R. Rodda,, D. Senyschen,, T. M. Baldwin,, L. A. Buckingham,, and S. J. Foote. 2002. Mice that are congenic for the char2 locus are susceptible to malaria. Infect. Immun. 70:47504753.
28. Casals-Pascual, C.,, S. Allen,, A. Allen,, O. Kai,, B. Lowe,, A. Pain,, and D. J. Roberts. 2001. Short report:codon 125 polymorphism of CD31 and susceptibility to malaria.Am.J.Trop. Med.Hyg. 65:736737.
29. Cattani, J.A.,, F.D. Gibson,, M. P. Alpers,, and G.G. Crane. 1987. Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea. Trans. R. Soc.Trop. Med. Hyg. 81:705709.
30. Chitnis, C. E.,, and L. H. Miller. 1994. Identification of the erythrocyte binding domains of Plasmodium vivax and Plasmodium knowlesi proteins involved in erythrocyte invasion. J. Exp. Med. 180:497506.
31. Chotivanich, K.,, R. Udomsangpetch,, K. Pattanapanyasat,, W. Chierakul,, J. Simpson,, S. Looareesuwan, and N.White. 2002.Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. Blood 100:11721176.
32. Clark, I. A.,, and K. A. Rockett. 1996. Nitric oxide and parasitic disease. Adv. Parasitol. 37:156.
33. Cockburn, I. A.,, M. J. Mackinnon,, A. O’Donnell,, S. J. Allen,, J. M. Moulds,, M. Baisor,, M. Bockarie,, J. C. Reeder,, and J. A. Rowe. 2004. A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc. Natl. Acad Sci. USA 101:272277.
34. Cooke, G. S.,, C. Aucan,, A. J. Walley,, S. Segal,, B. M. Greenwood,, D. P. Kwiatkowski,, and A.V. Hill. 2003.Association of Fcγ receptor IIa (CD32) polymorphism with severe malaria in West Africa. Am. J.Trop. Med. Hyg. 69:565568.
35. Diallo, D.A.,, O. K. Doumbo,, A. Dicko,, A. Guindo,, D. Coulibaly,, K. Kayentao,, A.A. Djimde,, M.A. Thera,, R. M. Fairhurst,, C.V. Plowe,, and T. E. Wellems. 2004. A comparison of anemia in hemoglobin C and normal hemoglobin A children with Plasmodium falciparum malaria. Acta Trop. 90:295299.
36. Elagib, A. A.,, A. O. Kider,, B. Akerstrom,, and M. I. Elbashir. 1998.Association of the haptoglobin phenotype (1-1) with falciparum malaria in Sudan. Trans. R. Soc.Trop. Med. Hyg. 92:309311.
37. Engwerda, C. R.,, T. L. Mynott,, S. Sawhney,, J. B. De Souza,, Q. D. Bickle,, and P. M. Kaye. 2002. Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha,is the principle mediator of murine cerebral malaria. J. Exp. Med. 195:13711377.
38. Facer, C.A. 1983. Merozoites of P. falciparum require glycophorin for invasion into red cells. Bull. Soc. Pathol. Exot. Filiales 76:463469.
39. Fernandez-Reyes, D.,, A. G. Craig,, S. A. Kyes,, N. Peshu,, R.W. Snow,, A. R. Berendt,, K. Marsh,, and C. I. Newbold. 1997.A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum. Mol. Genet. 6:13571360.
40. Flint, J.,, A.V. Hill,, D. K. Bowden,, S. J. Oppenheimer,, P. R. Sill,, S.W. Serjeantson,, J. Bana- Koiri,, K. Bhatia,, M. P. Alpers,, A. J. Boyce, et al. 1986. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature 321:744750.
41. Flori, L.,, S. Sawadogo,, C. Esnault,, N. F. Delahaye,, F. Fumoux,, and P. Rihet. 2003. Linkage of mild malaria to the major histocompatibility complex in families living in Burkina Faso. Hum. Mol. Genet. 12:375378.
42. Foo, L. C.,, V. Rekhraj,, G. L. Chiang,, and J.W. Mak. 1992. Ovalocytosis protects against severe malaria parasitemia in the Malayan aborigines. Am. J.Trop. Med. Hyg. 47:271275.
43. Foote, S. J.,, R.A. Burt,, T. M. Baldwin,, A. Presente,, A. W. Roberts,, Y. L. Laural,, A. M. Lew,, and V. M. Marshall. 1997. Mouse loci for malariainduced mortality and the control of parasitaemia. Nat. Genet. 17:380381.
44. Fortin, A.,, A. Belouchi,, M. F. Tam,, L. Cardon,, E. Skamene,, M. M. Stevenson,, and P. Gros. 1997.Genetic control of blood parasitaemia in mouse malaria maps to chromosome 8.Nat.Genet. 17:382383.
45. Fortin, A.,, L. R. Cardon,, M. Tam,, E. Skamene,, M. M. Stevenson,, and P. Gros. 2001. Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc. Natl. Acad. Sci. USA 98:1079310798.
46. Ganczakowski, M.,, M. Town,, D. K. Bowden,, T. J. Vulliamy,, A. Kaneko,, J. B. Clegg,, D. J. Weatherall,, and L. Luzzatto. 1995. Multiple glucose 6- phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (southwestern Pacific). Am. J. Hum. Genet. 56:294301.
47. Garcia, A.,, M. Cot,, J. P. Chippaux,, S. Ranque,, J. Feingold,, F. Demenais,, and L. Abel. 1998a. Genetic control of blood infection levels in human malaria: evidence for a complex genetic model.Am. J.Trop. Med. Hyg. 58:480488.
48. Garcia, A.,, S. Marquet,, B. Bucheton,, D. Hillaire,, M. Cot,, N. Fievet,, A. J. Dessein,, and L. Abel. 1998b. Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31-q33 chromosome region. Am. J.Trop. Med. Hyg. 58:705709.
49. Genton, B.,, F. al-Yaman,, C. S. Mgone,, N. Alexander,, M.M. Paniu,, M. P. Alpers,, and D. Mokela. 1995. Ovalocytosis and cerebral malaria. Nature 378:564565.
50. Gilbert, S. C.,, M. Plebanski,, S. Gupta,, J. Morris,, M. Cox,, M. Aidoo,, D. Kwiatkowski,, B. M. Greenwood,, H.C. Whittle,, and A.V. Hill. 1998. Association of malaria parasite population structure, HLA, and immunological antagonism. Science 279: 11731177.
51. Gilles, H. M.,, K. A. Fletcher,, R. G. Hendrickse,, R. Lindner,, S. Reddy,, and N. Allan. 1967. Glucose- 6-phosphate-dehydrogenase deficiency, sickling, and malaria in African children in south western Nigeria. Lancet 1:138140.
52. Grau, G. E.,, L. F. Fajardo,, P. F. Piguet,, B. Allet,, P. H. Lambert,, and P. Vassalli. 1987a.Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science 237:12101212.
53. Grau, G. E.,, D. Gretener,, and P. H. Lambert. 1987b. Prevention of murine cerebral malaria by low-dose cyclosporin A. Immunology 61:521525.
54. Grau, G. E.,, H. Heremans,, P. F. Piguet,, P. Pointaire,, P. H. Lambert,, A. Billiau,, and P. Vassalli. 1989. Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proc. Natl.Acad. Sci. USA 86:55725574.
55. Greenberg, J.,, and L. P. Kendrick. 1959. Resistance to malaria in hybrids between Swiss and certain other strains of mice. J. Parasitol. 45:263267.
56. Greenberg, J.,, E. M. Nadel,, and G. R. Coatney. 1954. Differences in survival of several inbred strains of mice and their hybrids infected with Plasmodium berghei. J. Infect. Dis. 95:114116.
57. Hill, A.V.,, C. E. Allsopp,, D. Kwiatkowski,, N. M. Anstey,, P. Twumasi,, P. A. Rowe,, S. Bennett,, D. Brewster,, A. J. McMichael,, and B. M. Greenwood. 1991. Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595600
58. Hill, A.V.,, J. Elvin,, A.C. Willis,, M. Aidoo,, C. E. Allsopp,, F. M. Gotch,, X. M. Gao,, M. Takiguchi,, B. M. Greenwood,, A. R. Townsend, et al. 1992. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360:434439.
59. Hobbs, M. R.,, V. Udhayakumar,, M. C. Levesque,, J. Booth,, J. M. Roberts,, A.N. Tkachuk,, A. Pole,, H. Coon,, S. Kariuki,, B. L. Nahlen,, E. D. Mwaikambo,, A. L. Lal,, D. L. Granger,, N. M. Anstey,, and J. B. Weinberg. 2002.A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children. Lancet 360:14681475.
60. Hunt, N. H.,, C. Driussi,, and L. Sai-Kiang. 2001. Haptoglobin and malaria. Redox Rep. 6:389392.
61. Hunt, N. H.,, N. Manduci,, and C. M. Thumwood. 1993.Amelioration of murine cerebral malaria by dietary restriction. Parasitology 107:471476.
62. Jayawardena, A. N.,, R. Mogil,, D. B. Murphy,, D. Burger,, and R. K. Gershon. 1983. Enhanced expression of H-2K and H-2D antigens on reticulocytes infected with Plasmodium yoelii. Nature 302:623626.
63. Jepson, A.,, F. Sisay-Joof,, W. Banya,, M. Hassan- King,, A. Frodsham,, S. Bennett,, A.V. Hill,, and H. Whittle. 1997. Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs.BMJ 315:9697.
64. Jepson, A.P.,, W.A. Banya,, F. Sisay-Joof,, M. Hassan- King,, S. Bennett,, and H. C. Whittle. 1995. Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children. J. Infect. Dis. 172:316319.
65. Juliger, S.,, M. Bongartz,, A. J. Luty,, P.G. Kremsner,, and J. F. Kun. 2003. Functional analysis of a promoter variant of the gene encoding the interferongamma receptor chain I.Immunogenetics 54:675680.
66. Kikuchi, M.,, S. Looareesuwan,, R. Ubalee,, O. Tasanor,, F. Suzuki,, Y. Wattanagoon,, K. Na- Bangchang,, A. Kimura,, M. Aikawa,, and K. Hirayama. 2001. Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais. Parasitol. Int. 50:235239.
67. Kitchen, S. F., 1949. Symptomatology: general considerations, p. 966994. In M.F. Boyd (ed.), Malariology. W. B. Saunders, Philadelphia, Pa.
68. Knight, J. C.,, B. J. Keating,, K. A. Rockett,, and D. P. Kwiatkowski. 2003. In vivo characterization of regulatory polymorphisms by allele-specific quantification of RNA polymerase loading. Nat. Genet. 33:469475.
69. Knight, J. C.,, I. Udalova,, A.V. Hill,, B. M. Greenwood,, N. Peshu,, K. Marsh,, and D. Kwiatkowski. 1999. A polymorphism that affects OCT- 1 binding to the TNF promoter region is associated with severe malaria. Nat. Genet. 22:145150.
70. Koch, O.,, A. Awomoyi,, S. Usen,, M. Jallow,, A. Richardson,, J. Hull,, M. Pinder,, M. Newport,, and D. Kwiatkowski. 2002. IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria. J. Infect. Dis. 185:16841687.
71. Kremsner, P. G.,, H. Grundmann,, S. Neifer,, K. Sliwa,, G. Sahlmuller,, B. Hegenscheid,, and U. Bienzle. 1991. Pentoxifylline prevents murine cerebral malaria. J. Infect. Dis. 164:605608.
72. Kun, J. F.,, J. Klabunde,, B. Lell,, D. Luckner,, M. Alpers,, J. May,, C. Meyer,, and P. G. Kremsner. 1999. Association of the ICAM-1Kilifi mutation with protection against severe malaria in Lambarene, Gabon. Am. J.Trop. Med. Hyg. 61:776779.
73. Kun, J. F.,, B. Mordmuller,, B. Lell,, L. G. Lehman,, D. Luckner,, and P. G. Kremsner. 1998. Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 351:265266.
74. Kun, J. F.,, B. Mordmuller,, D. J. Perkins,, J. May,, O. Mercereau-Puijalon,, M. Alpers,, J. B. Weinberg,, and P. G. Kremsner. 2001. Nitric oxide synthase 2(Lambarene) (G-954C), increased nitric oxide production, and protection against malaria. J. Infect. Dis. 184:330336.
75. Kwiatkowski, D.,, and P. Perlmann,. 1999. Inflammatory processes in the pathogenesis of malaria, p. 329362. In M. Wahlgen, and P. Perlmann (ed.), Malaria: Molecular and Clinical Aspects. Harwood Academic Publishers,The Netherlands.
76. Levesque, M.C.,, M. R. Hobbs,, N. M. Anstey,, T.N. Vaughn,, J.A. Chancellor,, A. Pole,, D. J. Perkins,, M.A. Misukonis,, S. J. Chanock,, D. L. Granger,, and J. B. Weinberg. 1999. Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria. J. Infect. Dis. 180:19942002.
77. Luoni, G.,, F. Verra,, B. Arca,, B. S. Sirima,, M. Troye- Blomberg,, M. Coluzzi,, D. Kwiatkowski,, and D. Modiano. 2001. Antimalarial antibody levels and IL4 polymorphism in the Fulani of West Africa. Genes Immun. 2:411414.
78. Luty, A. J.,, J. F. Kun,, and P. G. Kremsner. 1998. Mannose-binding lectin plasma levels and gene polymorphisms in Plasmodium falciparum malaria. J. Infect. Dis. 178:12211224.
79. Luzzatto, L.,, F.A. Usanga,, and S. Reddy. 1969. Glucose- 6-phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites. Science 164:839842.
80. Maier, A. G.,, M.T. Duraisingh,, J. C. Reeder,, S. S. Patel,, J. W. Kazura,, P. A. Zimmerman,, and A. F. Cowman. 2003. Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nat. Med. 9:8792.
81. Mayor, A.,, N. Bir,, R. Sawhney,, S. Singh,, P. Pattnaik,, S. K. Singh,, A. Sharma,, and C. E. Chitnis. 2005. Receptor-binding residues lie in central regions of Duffy-binding-like domains involved in red cell invasion and cytoadherence by malaria parasites. Blood 105:25572563.
82. McGuire, W.,, A. V. Hill,, C. E. Allsopp,, B. M. Greenwood,, and D. Kwiatkowski. 1994.Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 371:508510.
83. McGuire, W.,, J.C. Knight,, A.V. Hill,, C. E. Allsopp,, B. M. Greenwood,, and D. Kwiatkowski. 1999. Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. J. Infect. Dis. 179:287290.
84. Meyer, C. G.,, J. May,, A. J. Luty,, B. Lell,, and P. G. Kremsner. 2002. TNFα-308A associated with shorter intervals of Plasmodium falciparum reinfections. Tissue Antigens 59:287292.
85. Miller, L. H.,, S. J. Mason,, D. F. Clyde,, and M. H. McGinniss. 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N. Engl. J. Med. 295:302304.
86. Min-Oo, G.,, A. Fortin,, M. F. Tam,, P. Gros,, and M. M. Stevenson. 2004. Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model. Genes Immun. 5:168175.
87. Min-Oo, G.,, A. Fortin,, M. F. Tam,, A. Nantel,, M. M. Stevenson,, and P. Gros. 2003. Pyruvate kinase deficiency in mice protects against malaria. Nat. Genet. 35:357362.
88. Mockenhaupt, F. P.,, S. Ehrhardt,, S. Gellert,, R. N. Otchwemah,, E. Dietz,, S. D. Anemana,, and V. Bienzle. 2004. Alpha(+-thalassemia protects African children from severe malaria. Blood 104:20032006.
89. Modiano, D.,, A. Chiucchiuini,, V. Petrarca,, B. S. Sirima,, G. Luoni,, H. Perlmann,, F. Esposito,, and M. Coluzzi. 1998. Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina Faso. Am. J. Trop. Med. Hyg. 58:220224.
90. Modiano, D.,, A. Chiucchiuini,, V. Petrarca,, B. S. Sirima,, G. Luoni,, M. A. Roggero,, G. Corradin,, M. Coluzzi,, and F. Esposito. 1999. Interethnic differences in the humoral response to non-repetitive regions of the Plasmodium falciparum circumsporozoite protein.Am.J.Trop. Med.Hyg. 61:663667.
91. Modiano, D.,, G. Luoni,, B. S. Sirima,, A. Lanfrancotti,, V. Petrarca,, F. Cruciani,, J. Simpore,, B. M. Ciminelli,, E. Foglietta,, P. Grisanti,, I. Bianco,, G. Modiano,, and M. Coluzzi. 2001a.The lower susceptibility to Plasmodium falciparum malaria of Fulani of Burkina Faso (west Africa) is associated with low frequencies of classic malaria-resistance genes. Trans. R. Soc.Trop. Med. Hyg. 95:149152.
92. Modiano, D.,, G. Luoni,, B. S. Sirima,, J. Simpore,, F. Verra,, A. Konate,, E. Rastrelli,, A. Olivieri,, C. Calissano,, G. M. Paganotti,, L. D’Urbano,, I. Sanou,, A. Sawadogo,, G. Modiano,, and M. Coluzzi. 2001b.Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature 414:305308.
93. Modiano, D.,, V. Petrarca,, B. S. Sirima,, I. Nebie,, D. Diallo,, F. Esposito,, and M. Coluzzi. 1996. Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups. Proc. Natl. Acad. Sci. USA 93:1320613211.
94. Morahan, G.,, C. S. Boutlis,, D. Huang,, A. Pain,, J. R. Saunders,, M. R. Hobbs,, D. L. Granger,, J. B. Weinberg,, N. Peshu,, E. D. Mwaikambo,, K. Marsh,, D. J. Roberts,, and N. M. Anstey. 2002. A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production. Genes Immun. 3:414418.
95. Nadel, E.,, J. Greenberg,, G. E. Jay,, and G. R. Coatney. 1955. Backcross studies on the genetics of resistance to malaria in mice. Genetics 40:620626.
96. Nagayasu, E.,, M. Ito,, M. Akaki,, Y. Nakano,, M. Kimura,, S. Looareesuwan,, and M. Aikawa. 2001. CR1 density polymorphism on erythrocytes of falciparum malaria patients in Thailand. Am. J. Trop. Med. Hyg. 64:15.
97. Nagayasu, E.,, K. Nagakura,, M. Akaki,, G. Tamiya,, S. Makino,, Y. Nakano,, M. Kimura,, and M. Aikawa. 2002.Association of a determinant on mouse chromosome 18 with experimental severe Plasmodium berghei malaria. Infect. Immun. 70:512516.
98. Neill, A. L.,, T. Chan-Ling,, and N. H. Hunt. 1993. Comparisons between microvascular changes in cerebral and non-cerebral malaria in mice, using the retinal whole-mount technique. Parasitology 107:477487.
99. Neill, A. L.,, and N. H. Hunt. 1992. Pathology of fatal and resolving Plasmodium berghei cerebral malaria in mice. Parasitology 105:165175.
100. Ohashi, J.,, I. Naka,, J. Patarapotikul,, H. Hananantachai,, G. Brittenham,, S. Looareesuwan,, A.G. Clark,, and K. Tokunaga. 2004. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am. J. Hum. Genet. 74:11981208.
101. Ohno, T.,, and M. Nishimura. 2004. Detection of a new cerebral malaria susceptibility locus, using CBA mice. Immunogenetics 56:675678.
102. Omi, K.,, J. Ohashi,, J. Patarapotikul,, H. Hananantachai,, I. Naka,, S. Looareesuwan,, and K. Tokunaga. 2003. CD36 polymorphism is associated with protection from cerebral malaria.Am.J.Hum.Genet. 72:364374.
103. Omi, K.,, J. Ohashi,, J. Patarapotikul,, H. Hananantachai,, I. Naka,, S. Looareesuwan,, and K. Tokunaga. 2002. Fcγ receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria. Parasitol. Int. 51:361366.
104. Orlandi, P.A.,, F.W. Klotz,, and J.D. Haynes. 1992. A malaria invasion receptor, the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum recognizes the terminal Neu5Ac((2-3)Gal- sequences of glycophorin A. J. Cell Biol. 116:901909.
105. Pain, A.,, B.C. Urban,, O. Kai,, C. Casals-Pascual,, J. Shafi,, K. Marsh,, and D. J. Roberts. 2001. A nonsense mutation in Cd36 gene is associated with protection from severe malaria. Lancet 357:15021503.
106. Pasvol, G.,, D. J. Weatherall,, and R. J. Wilson. 1978. Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria. Nature 274:701703.
107. Patel, S. S.,, C. L. King,, C. S. Mgone,, J.W. Kazura,, and P. A. Zimmerman. 2004. Glycophorin C (Gerbich antigen blood group) and band 3 polymorphisms in two malaria holoendemic regions of Papua New Guinea. Am. J. Hematol. 75:15.
108. Patel, S. S.,, R. K. Mehlotra,, W. Kastens,, C. S. Mgone,, J.W. Kazura,, and P. A. Zimmerman. 2001. The association of the glycophorin C exon 3 deletion with ovalocytosis and malaria susceptibility in the Wosera, Papua New Guinea. Blood 98:34893491.
109. Quaye, I. K.,, F. A. Ekuban,, B. Q. Goka,, V. Adabayeri,, J.A. Kurtzhals,, B. Gyan,, N.A. Ankrah,, L. Hviid,, and B.D. Akanmori. 2000. Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria. Trans. R. Soc.Trop. Med. Hyg. 94:216219.
110. Rest, J. R. 1982. Cerebral malaria in inbred mice. I.A new model and its pathology. Trans.R. Soc.Trop. Med. Hyg. 76:410415.
111. Rihet, P.,, L. Abel,, Y. Traore,, T. Traore-Leroux,, C. Aucan,, and F. Fumoux. 1998a. Human malaria: segregation analysis of blood infection levels in a suburban area and a rural area in Burkina Faso. Genet. Epidemiol. 15:435450.
112. Rihet, P.,, L. Flori,, F. Tall,, A. S. Traore,, and F. Fumoux. 2004. Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. Hum. Mol. Genet. 13:16.
113. Rihet, P.,, Y. Traore,, L. Abel,, C. Aucan,, T. Traore- Leroux,, and F. Fumoux. 1998b. Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5q31-q33.Am.J.Hum. Genet. 63:498505.
114. Rowe, J. A.,, J. M. Moulds,, C. I. Newbold,, and L. H. Miller. 1997. P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388:292295.
115. Ruwende, C.,, S. C. Khoo,, R.W. Snow,, S.N. Yates,, D. Kwiatkowski,, S. Gupta,, P. Warn,, C. E. Allsopp,, S. C. Gilbert,, N. Peschu, et al. 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376:246249.
116. Sabeti, P.,, S. Usen,, S. Farhadian,, M. Jallow,, T. Doherty,, M. Newport,, M. Pinder,, R. Ward,, and D. Kwiatkowski. 2002a. CD40L association with protection from severe malaria. Genes Immun. 3:286291.
117. Sabeti, P. C.,, D. E. Reich,, J. M. Higgins,, H. Z. Levine,, D. J. Richter,, S. F. Schaffner,, S. B. Gabriel,, J. V. Platko,, N. J. Patterson,, G. J. McDonald,, H. C. Ackerman,, S. J. Campbell,, D. Altshuler,, R. Cooper,, D. Kwiatkowski,, R. Ward,, and E. S. Lander. 2002b. Detecting recent positive selection in the human genome from haplotype structure. Nature 419:832837.
118. Sayles, P.C.,, and D. L. Wassom. 1988. Immunoregulation in murine malaria. Susceptibility of inbred mice to infection with Plasmodium yoelii depends on the dynamic interplay of host and parasite genes. J. Immunol. 141:241248.
119. Schofield, L.,, M. C. Hewitt,, K. Evans,, M. A. Siomos,, and P. H. Seeberger. 2002. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature 418:785789.
120. Shear, H. L.,, E. F. Roth, Jr.,, M. E. Fabry,, F. D. Costantini,, A. Pachnis,, A. Hood,, and R. L. Nagel. 1993. Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria. Blood 81:222226.
121. Sherman, I.W.,, S. Eda,, and E. Winograd. 2003. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect. 5:897909.
122. Shi, Y. P.,, B. L. Nahlen,, S. Kariuki,, K. B. Urdahl,, P. D. McElroy,, J. M. Roberts,, and A. A. Lal. 2001. Fcγ receptor IIa (CD32) polymorphism is associated with protection of infants against highdensity Plasmodium falciparum infection. VII. Asembo Bay Cohort Project. J. Infect. Dis. 184:107111.
123. Sokhna, C. S.,, C. Rogier,, A. Dieye,, and J. F. Trape. 2000. Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission. Am. J.Trop. Med. Hyg. 62:266270.
124. Stevenson, M. M.,, J. J. Lyanga,, and E. Skamene. 1982. Murine malaria: genetic control of resistance to Plasmodium chabaudi. Infect. Immun. 38:8088.
125. Stevenson, M. M.,, and E. M. Riley. 2004. Innate immunity to malaria. Nat. Rev. Immunol. 4:169180.
126. Stevenson, M. M.,, and E. Skamene. 1985. Murine malaria: resistance of AXB/BXA recombinant inbred mice to Plasmodium chabaudi. Infect.Immun. 47:452456.
127. Stirnadel, H. A.,, F. Al-Yaman,, B. Genton,, M. P. Alpers,, and T. A. Smith. 2000a. Assessment of different sources of variation in the antibody responses to specific malaria antigens in children in Papua New Guinea. Int. J. Epidemiol. 29:579586.
Stirnadel, H. A.,, H. P. Beck,, M. P. Alpers,, and T. A. Smith. 2000.b. Genetic analysis of IgG subclass responses against RESA and MSP2 of Plasmodium falciparum in adults in Papua New Guinea. Epidemiol. Infect. 124:153162.
Stirnadel, H. A.,, H. P. Beck,, M. P. Alpers,, and T. A. Smith. 1999.a. Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea. Genet. Epidemiol. 17:1634.
130. Stirnadel, H. A.,, M. Stockle,, I. Felger,, T. Smith,, M. Tanner,, and H. P. Beck. 1999b. Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania. Trop. Med. Int. Health 4:187193.
131. Taylor, T. E.,, W. J. Fu,, R. A. Carr,, R. O. Whitten,, J. S. Mueller,, N. G. Fosiko,, S. Lewallen,, N. G. Liomba,, and M. E. Molyneux. 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat. Med. 10:143145.
132. Thumwood, C. M.,, N. H. Hunt,, I. A. Clark,, and W. B. Cowden. 1988. Breakdown of the blood brain barrier in murine cerebral malaria. Parasitology 96:579589.
133. Tishkoff, S. A.,, R. Varkonyi,, N. Cahinhinan,, S. Abbes,, G. Argyropoulos,, G. Destro-Bisol,, A. Drousiotou,, B. Dangerfield,, G. Lefranc,, J. Loiselet,, A. Piro,, M. Stoneking,, A. Tagarelli,, G. Tagarelli,, E. H. Touma,, S. M. Williams,, and A.G. Clark. 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293:455462.
134. Tournamille, C.,, Y. Colin,, J. P. Cartron,, and C. Le Van Kim. 1995. Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat. Genet. 10:224228.
135. Treutiger, C. J.,, A. Heddini,, V. Fernandez,, W. A. Muller,, and M. Wahlgren. 1997. PECAM- 1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat. Med. 3:14051408.
136. Urban, B. C.,, D. J. Ferguson,, A. Pain,, N. Willcox,, M. Plebanski,, J. M. Austyn,, and D. J. Roberts. 1999. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400:7377.
137. Urban, B. C.,, N. Willcox,, and D. J. Roberts. 2001. A role for CD36 in the regulation of dendritic cell function. Proc. Natl. Acad. Sci. USA 98:87508755.
138. Usanga, E. A.,, and L. Luzzatto. 1985. Adaptation of Plasmodium falciparum to glucose 6-phosphate dehydrogenase-deficient host red cells by production of parasite-encoded enzyme. Nature 313:793795.
139. Vigario, A.M.,, E. Belnoue,, A. Cumano,, M. Marussig,, F. Miltgen,, I. Landau,, D. Mazier,, I. Gresser,, and L. Renia. 2001. Inhibition of Plasmodium yoelii blood-stage malaria by interferon alpha through the inhibition of the production of its target cell, the reticulocyte. Blood 97:39663971.
140. Walley, A. J.,, C. Aucan,, D. Kwiatkowski,, and A.V. Hill. 2004. Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case-control study. Eur. J. Hum. Genet. 12:132138.
141. Wang, H.Y.,, H. Tang,, C. K. Shen,, and C. I. Wu. 2003. Rapidly evolving genes in human. I.The glycophorins and their possible role in evading malaria parasites. Mol. Biol. Evol. 20:17951804.
142. Wattavidanage, J.,, R. Carter,, K. L. Perera,, A. Munasingha,, S. Bandara,, D. McGuinness,, A. R. Wickramasinghe,, H. K. Alles,, K. N. Mendis,, and S. Premawansa. 1999.TNFα*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans. Clin. Exp. Immunol. 115:350355.
143. Williams, T. N.,, K. Maitland,, S. Bennett,, M. Ganczakowski,, T. E. Peto,, C. I. Newbold,, D. K. Bowden,, D. J. Weatherall,, and J. B. Clegg. 1996. High incidence of malaria in alpha-thalassaemic children. Nature 383:522525.
144. Williams, T. N.,, S. Wambua,, S. Uyoga,, A. Macharia,, J. K. Mwacharo,, C. R. Newton,, and K. Maitland. 2005. Both homozygous and heterozygous α+-thalassemia protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 106:368371.
145. Yazdani, S. S.,, A. R. Shakri,, P. Mukherjee,, S. K. Baniwal,, and C. E. Chitnis. 2004. Evaluation of immune responses elicited in mice against a recombinant malaria vaccine based on Plasmodium vivax Duffy binding protein. Vaccine 22:37273737.
146. Zimmerman, P. A.,, J. Fitness,, J. M. Moulds,, D.T. McNamara,, L. J. Kasehagen,, J. A. Rowe,, and A.V. Hill. 2003. CR1 Knops blood group alleles are not associated with severe malaria in the Gambia. Genes Immun. 4:368373.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error