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    A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults

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    Author
    Randall, LM; Kenangalem, E; Lampah, DA; Tjitra, E; Mwaikambo, ED; Handojo, T; Piera, KA; Zhao, ZZ; Rivera, FDL; Zhou, Y; ...
    Date
    2010-10-29
    Source Title
    Malaria Journal
    Publisher
    BMC
    University of Melbourne Author/s
    Randall, Louise; Haque, Ashraful
    Affiliation
    Medicine and Radiology
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Randall, L. M., Kenangalem, E., Lampah, D. A., Tjitra, E., Mwaikambo, E. D., Handojo, T., Piera, K. A., Zhao, Z. Z., Rivera, F. D. L., Zhou, Y., McSweeney, K. M., Le, L., Amante, F. H., Haque, A., Stanley, A. C., Woodberry, T., Salwati, E., Granger, D. L., Hobbs, M. R. ,... Engwerda, C. R. (2010). A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults. MALARIA JOURNAL, 9 (1), https://doi.org/10.1186/1475-2875-9-302.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257144
    DOI
    10.1186/1475-2875-9-302
    Abstract
    BACKGROUND: Severe malaria (SM) syndromes caused by Plasmodium falciparum infection result in major morbidity and mortality each year. However, only a fraction of P. falciparum infections develop into SM, implicating host genetic factors as important determinants of disease outcome. Previous studies indicate that tumour necrosis factor (TNF) and lymphotoxin alpha (LTα) may be important for the development of cerebral malaria (CM) and other SM syndromes. METHODS: An extensive analysis was conducted of single nucleotide polymorphisms (SNPs) in the TNF, LTA and LTB genes in highland Papuan children and adults, a population historically unexposed to malaria that has migrated to a malaria endemic region. Generated P-values for SNPs spanning the LTA/TNF/LTB locus were corrected for multiple testing of all the SNPs and haplotype blocks within the region tested through 10,000 permutations. A global P-value of < 0.05 was considered statistically significant. RESULTS: No associations between SNPs in the TNF/LTA/LTB locus and susceptibility to SM in highland Papuan children and adults were found. CONCLUSIONS: These results support the notion that unique selective pressure on the TNF/LTA/LTB locus in different populations has influenced the contribution of the gene products from this region to SM susceptibility.

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