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Open Access 01-12-2010 | Research

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

Authors: Louise M Randall, Enny Kenangalem, Daniel A Lampah, Emiliana Tjitra, Esther D Mwaikambo, Tjandra Handojo, Kim A Piera, Zhen Z Zhao, Fabian de Labastida Rivera, Yonghong Zhou, Karli M McSweeney, Lien Le, Fiona H Amante, Ashraful Haque, Amanda C Stanley, Tonia Woodberry, Ervi Salwati, Donald L Granger, Maurine R Hobbs, Ric N Price, J Brice Weinberg, Grant W Montgomery, Nicholas M Anstey, Christian R Engwerda

Published in: Malaria Journal | Issue 1/2010

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 (LTα) 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 P-value 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.

Available only for authorised users

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Title: A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults
Authors: Louise M Randall
Enny Kenangalem
Daniel A Lampah
Emiliana Tjitra
Esther D Mwaikambo
Tjandra Handojo
Kim A Piera
Zhen Z Zhao
Fabian de Labastida Rivera
Yonghong Zhou
Karli M McSweeney
Lien Le
Fiona H Amante
Ashraful Haque
Amanda C Stanley
Tonia Woodberry
Ervi Salwati
Donald L Granger
Maurine R Hobbs
Ric N Price
J Brice Weinberg
Grant W Montgomery
Nicholas M Anstey
Christian R Engwerda
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Malaria Journal / Issue 1/2010
Electronic ISSN: 1475-2875
DOI: https://doi.org/10.1186/1475-2875-9-302

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