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

Louise Randall, E Kenangalem, Daniel Lampah, E Tjitra, E Mwaikambo, Tjandra Handojo, Kim Piera, 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 PriceJoe 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 (LT) 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
    Number of pages9
    JournalMalaria Journal
    Volume9
    Issue number1
    DOIs
    Publication statusPublished - 2010

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  • Cite this

    Randall, L., Kenangalem, E., Lampah, D., Tjitra, E., Mwaikambo, E., Handojo, T., Piera, K., Zhao, Z., de Labastida Rivera, F., Zhou, Y., McSweeney, K., Le, L., Amante, F., Haque, A., Stanley, A., Woodberry, T., Salwati, E., Granger, D., Hobbs, M., ... Engwerda, C. (2010). A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults. Malaria Journal, 9(1), [302]. https://doi.org/10.1186/1475-2875-9-302