A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults
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Date
2010
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Publisher
Malaria journal
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.
Description
Keywords
severe malaria, children and adults, Highland Papuan
Citation
Randall, L.M., Kenangalem, E., Lampah, D.A., Tjitra, E., Mwaikambo, E.D., Handojo, T., Piera, K.A., Zhao, Z.Z., de Labastida Rivera, F., Zhou, Y. and McSweeney, K.M., 2010. A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults. Malaria journal, 9(1), p.302.