Malaria Journal (Oct 2010)

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

  • 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

DOI
https://doi.org/10.1186/1475-2875-9-302
Journal volume & issue
Vol. 9, no. 1
p. 302

Abstract

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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 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.