Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

Louise Randall, Enny Kenangalem, Daniel Lampah, Emiliana Tjitra, 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

    Research output: Contribution to journalArticle

    Abstract

    Background: Age and host genetics are important determinants of malaria severity. Lymphotoxin-? (LT?) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa production contribute to other acute vascular diseases and may contribute to malaria pathogenesis.

    Methods: We tested the association between rs7291467, a single-nucleotide polymorphism (SNP) in the LT?related gene encoding galectin-2 (LGALS2), disease severity, and function in a case-control study of ethnic Highland Papuan adults and children with SM (n = 380) and asymptomatic malaria-exposed controls (n = 356) originating from a non-malaria-endemic region but residing in a lowland malaria-endemic area of Papua, Indonesia.

    Results: The LGALS2 SNP showed a significant association with susceptibility to SM (including CM), in children (odds ratio, 2.02 [95% confidence interval, 1.14-3.57]) but not in adults. In SM, the C allele at rs7291467 was associated with enhanced galectin-2 transcript levels. In a separate group of Tanzanian children originating from a malaria-endemic region, we found preservation of the major ancestral LGALS2 allele and no association with susceptibility to CM.

    Conclusions: Results suggest differences in the inflammatory contribution to the development of SM between children and adults in the same population and potential differences between individuals originating from malariaendemic and non-malaria-endemic areas. 
    Original languageEnglish
    Pages (from-to)117-124
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume202
    DOIs
    Publication statusPublished - 1 Jul 2010

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    Randall, L., Kenangalem, E., Lampah, D., Tjitra, E., Mwaikambo, E., Handojo, T., Piera, K., Zhao, Z. Z., Rivera, F. D. L., Zhou, Y., McSweeney, K., Le, L., Amante, F., Haque, A., Stanley, A., Woodberry, T., Salwati, E., Granger, D., Hobbs, M., ... Engwerda, C. (2010). Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans. Journal of Infectious Diseases, 202, 117-124. https://doi.org/10.1086/653125