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    Toll-like receptor polymorphisms in malaria-endemic populations

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    Authors
    Greene, Jennifer A.
    Moormann, Ann M.
    Vulule, John M.
    Bockarie, Moses J.
    Zimmerman, Peter A.
    Kazura, James W.
    UMass Chan Affiliations
    Department of Pediatrics
    Department of Quantitative Health Sciences
    Document Type
    Journal Article
    Publication Date
    2009-03-26
    Keywords
    Animals
    Endemic Diseases
    *Genetic Predisposition to Disease
    Genotype
    Humans
    Kenya
    Malaria, Falciparum
    Membrane Glycoproteins
    North America
    Papua New Guinea
    Plasmodium falciparum
    Polymerase Chain Reaction
    Polymorphism, Single Nucleotide
    Receptors, Interleukin-1
    Toll-Like Receptors
    Biostatistics
    Epidemiology
    Health Services Research
    Immunology and Infectious Disease
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    Abstract
    BACKGROUND: Toll-like receptors (TLR) and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic. METHODS: A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL) single nucleotide polymorphisms (SNPs), and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic) or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity. RESULTS: The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD) and Hemoglobin S (HbS) in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations. CONCLUSION: Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective pressure from malaria or any other infectious agents in these populations.
    Source
    Malar J. 2009 Mar 24;8:50. Link to article on publisher's site
    DOI
    10.1186/1475-2875-8-50
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/47267
    PubMed ID
    19317913
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1186/1475-2875-8-50
    Scopus Count
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