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 Price & 4 others J Brice Weinberg, Grant Montgomery, Nicholas Anstey, Christian Engwerda

    Research output: Contribution to journalArticleResearchpeer-review

    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

    Fingerprint

    Galectin 2
    Malaria
    Cerebral Malaria
    Single Nucleotide Polymorphism
    Alleles
    Lymphotoxin-alpha
    Indonesia
    Acute Disease
    Vascular Diseases
    Individuality
    Genes

    Cite this

    Randall, L., Kenangalem, E., Lampah, D., Tjitra, E., Mwaikambo, E., Handojo, T., ... 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
    Randall, Louise ; Kenangalem, Enny ; Lampah, Daniel ; Tjitra, Emiliana ; Mwaikambo, Esther ; Handojo, Tjandra ; Piera, Kim ; Zhao, Zhen Zhen ; Rivera, Fabian de Labastida ; Zhou, Yonghong ; McSweeney, Karli ; Le, Lien ; Amante, Fiona ; Haque, Ashraful ; Stanley, Amanda ; Woodberry, Tonia ; Salwati, Ervi ; Granger, Donald ; Hobbs, Maurine ; Price, Ric ; Weinberg, J Brice ; Montgomery, Grant ; Anstey, Nicholas ; Engwerda, Christian. / Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans. In: Journal of Infectious Diseases. 2010 ; Vol. 202. pp. 117-124.
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    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. ",
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    author = "Louise Randall and Enny Kenangalem and Daniel Lampah and Emiliana Tjitra and Esther Mwaikambo and Tjandra Handojo and Kim Piera and Zhao, {Zhen Zhen} and Rivera, {Fabian de Labastida} and Yonghong Zhou and Karli McSweeney and Lien Le and Fiona Amante and Ashraful Haque and Amanda Stanley and Tonia Woodberry and Ervi Salwati and Donald Granger and Maurine Hobbs and Ric Price and Weinberg, {J Brice} and Grant Montgomery and Nicholas Anstey and Christian Engwerda",
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    Randall, L, Kenangalem, E, Lampah, D, Tjitra, E, Mwaikambo, E, Handojo, T, Piera, K, Zhao, ZZ, Rivera, FDL, Zhou, Y, McSweeney, K, Le, L, Amante, F, Haque, A, Stanley, A, Woodberry, T, Salwati, E, Granger, D, Hobbs, M, Price, R, Weinberg, JB, Montgomery, G, Anstey, N & Engwerda, C 2010, 'Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans', Journal of Infectious Diseases, vol. 202, pp. 117-124. https://doi.org/10.1086/653125

    Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans. / Randall, Louise; Kenangalem, Enny; Lampah, Daniel; Tjitra, Emiliana; Mwaikambo, Esther; Handojo, Tjandra; Piera, Kim; Zhao, Zhen Zhen; Rivera, Fabian de Labastida; Zhou, Yonghong; McSweeney, Karli; Le, Lien; Amante, Fiona; Haque, Ashraful; Stanley, Amanda; Woodberry, Tonia; Salwati, Ervi; Granger, Donald; Hobbs, Maurine; Price, Ric; Weinberg, J Brice; Montgomery, Grant; Anstey, Nicholas; Engwerda, Christian.

    In: Journal of Infectious Diseases, Vol. 202, 01.07.2010, p. 117-124.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans

    AU - Randall, Louise

    AU - Kenangalem, Enny

    AU - Lampah, Daniel

    AU - Tjitra, Emiliana

    AU - Mwaikambo, Esther

    AU - Handojo, Tjandra

    AU - Piera, Kim

    AU - Zhao, Zhen Zhen

    AU - Rivera, Fabian de Labastida

    AU - Zhou, Yonghong

    AU - McSweeney, Karli

    AU - Le, Lien

    AU - Amante, Fiona

    AU - Haque, Ashraful

    AU - Stanley, Amanda

    AU - Woodberry, Tonia

    AU - Salwati, Ervi

    AU - Granger, Donald

    AU - Hobbs, Maurine

    AU - Price, Ric

    AU - Weinberg, J Brice

    AU - Montgomery, Grant

    AU - Anstey, Nicholas

    AU - Engwerda, Christian

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    N2 - 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. 

    AB - 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. 

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    Randall L, Kenangalem E, Lampah D, Tjitra E, Mwaikambo E, Handojo T et al. Age-Related susceptibility to severe Malaria associated with Galectin-2 in Highland Papuans. Journal of Infectious Diseases. 2010 Jul 1;202:117-124. https://doi.org/10.1086/653125