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

Randall, Louise M., Kenangalem, Enny, Lampah, Daniel A., Tjitra, Emiliana, Mwaikambo, Esther D., Handojo, Tjandra, Piera, Kim A., Zhao, Zhen Z., Labastida Rivera, Fabian de, Zhou, Yonghong, McSweeney, Karli M., Le, Lien, Amante, Fiona H., Haque, Ashraful, Stanley, Amanda C., Woodberry, Tonia, Salwati, Ervi, Granger, Donald L., Price, Ric N., Anstey, Nicholas M. and et al. (2010). A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults. Malaria Journal,9:302-310.

Document type: Journal Article
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IRMA ID 81704288xPUB508
NHMRC Grant No. 290208
Title A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults
Author Randall, Louise M.
Kenangalem, Enny
Lampah, Daniel A.
Tjitra, Emiliana
Mwaikambo, Esther D.
Handojo, Tjandra
Piera, Kim A.
Zhao, Zhen Z.
Labastida Rivera, Fabian de
Zhou, Yonghong
McSweeney, Karli M.
Le, Lien
Amante, Fiona H.
Haque, Ashraful
Stanley, Amanda C.
Woodberry, Tonia
Salwati, Ervi
Granger, Donald L.
Price, Ric N.
Anstey, Nicholas M.
et al.
Journal Name Malaria Journal
Publication Date 2010
Volume Number 9
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Start Page 302
End Page 310
Total Pages 9
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
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 (LTa) 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 Pvalue 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.
Keywords TNF/LTA/LTB locus
Plasmodium falciparum
cerebral malaria (CM)
tumour necrosis factor (TNF)
lymphotoxin alpha
DOI   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)

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