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

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...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Granger Donald L, Salwati Ervi, Woodberry Tonia, Stanley Amanda C, Haque Ashraful, Amante Fiona H, Le Lien, McSweeney Karli M, Zhou Yonghong, de Labastida Rivera Fabian, Zhao Zhen Z, Piera Kim A, Handojo Tjandra, Mwaikambo Esther D, Tjitra Emiliana, Lampah Daniel A, Kenangalem Enny, Randall Louise M, Hobbs Maurine R, Price Ric N, Weinberg J Brice, Montgomery Grant W, Anstey Nicholas M, Engwerda Christian R
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2010
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Infectious and parasitic diseases
RC109-216
Arctic
Online Access:https://doi.org/10.1186/1475-2875-9-302
https://doaj.org/article/f096307c2f824df093cc062c9561934b
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Summary: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 (LTĪ±) 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.

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