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

Louise Randall, Enny Kenangalem, Daniel Lampah, Emiliana Tijitra, Esther Mwaikambo, Tjandra Handojo, Kim Piera, Zhen Zhen Zhao, Fabian de Labastida Rivera, Yonghong Zhou, Karli McSweeney, Lien Le, Fiona Amante, Ashraful Haque, Amanda Stanley, Tonia Woodberry, Ervi Salwati, Donald Granger, Maurine Hobbs, Ric PriceJ Brice Weinberg, Grant Montgomery, Nicholas Anstey, Christian Engwerda

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    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.

    Original languageEnglish
    Article number302
    Pages (from-to)1-9
    Number of pages9
    JournalMalaria Journal
    Volume9
    DOIs
    Publication statusPublished - 29 Oct 2010

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