Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans

Randall, Louise M., Kenangalem, Enny, Lampah, Daniel A., Tjitra, Emiliana, Mwaikambo, Esther D., Handojo, Tjandra, Piera, Kim A., Zhao, Zhen Zhen, Rivera, Fabian de Labastida, Zhou, Yonghong, McSweeney, Karli M., Le, Lien, Amante, Fiona H., Haque, Ashraful, Stanley, Amanda C., Woodberry, Tonia, Salwati, Ervi, Granger, Donald L., Hobbs, Maurine R., Price, Ric N., Weinberg, J. Brice, Montgomery, Grant W., Anstey, Nicholas M. and Engwerda, Christian R. (2010) Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans. Journal of Infectious Diseases, 202 1: 117-124.

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Author Randall, Louise M.
Kenangalem, Enny
Lampah, Daniel A.
Tjitra, Emiliana
Mwaikambo, Esther D.
Handojo, Tjandra
Piera, Kim A.
Zhao, Zhen Zhen
Rivera, Fabian de Labastida
Zhou, Yonghong
McSweeney, Karli M.
Le, Lien
Amante, Fiona H.
Haque, Ashraful
Stanley, Amanda C.
Woodberry, Tonia
Salwati, Ervi
Granger, Donald L.
Hobbs, Maurine R.
Price, Ric N.
Weinberg, J. Brice
Montgomery, Grant W.
Anstey, Nicholas M.
Engwerda, Christian R.
Title Age-related susceptibility to severe malaria associated with galectin-2 in highland Papuans
Journal name Journal of Infectious Diseases  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2010-07
Sub-type Article
DOI 10.1086/653125
Volume number 202
Issue number 1
ISSN 0022-1899; 1537-6613
Start page 117
End page 124
Total pages 8
Place of publication Chicago, IL, U.S.A.
Publisher University of Chicago Press
Collection year 2011
Language eng
Formatted abstract Background.
Age and host genetics are important determinants of malaria severity. Lymphotoxin-α (LTα) 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 LTαrelated 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. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Keyword Tumor-necrosis-factor
Nitric-oxide Synthase
Plasmodium-falciparum Malaria
Murine Cerebral Malaria
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 25 May, 2010.

Document type: Journal Article
Sub-type: Article
Collections: Official 2011 Collection
School of Population Health Publications
School of Medicine Publications
 
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