Gene polymorphism effects

Gene/polymorphism	Effect/association	Theoretical mechanism	Ref.
LTA + 80	Parasitemia reduction	Lymphotoxin production	[1]
GNAS	Severe malaria	Red cell signaling; invasion inhibition	[2]
iNOS	Severe malaria	Decreased iNOS	[3]
Pyruvate kinase	Infection	Unknown	[4]
ABO glycosyltransferase	Severe malaria anemia	Decreased resetting of red blood cells	[5]
Toll-like receptors (TLR-1, -6, and -9)	Malaria and high parasitemia	Innate immunity	[6]
FLT1	Placental malaria	Unknown	[7]
TIM1	Cerebral malaria	Induction of Th2 antiinflammatory responses	[8]
IL-10	Severe malaria anemia	Antiinflammatory activity of enhanced IL-10 production	[9]
CR-1 (promoter)	Cerebral malaria	Increased clearance of infected cells	[10,11]

LTA: lymphotoxin-alpha; iNOS: inducible nitric oxide synthase; IL: interleukin; CR: complement receptor.

1. Barbier M, et al. Family-based association of a low producing lymphotoxin-alpha allele with reduced Plasmodium falciparum parasitemia. Microbes Infect 2008; 10:673.
2. Auburn S, et al. Association of the GNAS locus with severe malaria. Human Genetics 2008; 124:499.
3. Dhangadamajhi G, et al. The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection. Parasitology Research.
4. Durand PM, Coetzer TM. Pyruvate kinase deficiency protects against malaria in humans. Haematologica 2008; 93:939.
5. Fry AE, et al. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria. Hum Mol Genet 2008; 17:567.
6. Leoratti FM, et al. Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria. J Infect Dis 2008; 198:772.
7. Muehlenbachs A, et al. Natural selection of FLT1 alleles and their association with malaria resistance in utero. Proc Natl Acad Sci U S A 2008; 105:14488.
8. Nuchnoi P, et al. Significant Association Between TIM1 Promoter Polymorphisms and Protection Against Cerebral malaria in Thailand. Annals of Human Genetics 2008; 72:327.
9. Ouma C, et al. Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production. Hum Genet 2008; 124:515.
10. Cockburn IA, et al. A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc Natl Acad Sci U S A 2004; 101:272.
11. Teeranaipong P, et al. A functional single-nucleotide polymorphism in the CR1 promoter region contributes to protection against cerebral malaria. J Infect Dis 2008; 198:1880.

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Gene polymorphism effects