Human Genetics

, Volume 125, Issue 1, pp 105–109

A genetic association study in the Gambia using tagging polymorphisms in the major histocompatibility complex class III region implicates a HLA-B associated transcript 2 polymorphism in severe malaria susceptibility

  • Mahamadou Diakite
  • Taane G. Clark
  • Sarah Auburn
  • Susana Campino
  • Andrew E. Fry
  • Angela Green
  • Andrew P. Morris
  • Anna Richardson
  • Muminatou Jallow
  • Fatou Sisay-Joof
  • Margaret Pinder
  • Dominic P. Kwiatkowski
  • Kirk A. Rockett
Short Report

Abstract

The tumour necrosis factor (TNF) gene and other genes flanking it in the major histocompatibility complex (MHC) class III region are potentially important mediators of both immunity and pathogenesis of malaria. We investigated the association of severe malaria with 11 haplotype tagging-polymorphisms for 11 MHC class III candidate genes, including TNF, lymphotoxin alpha (LTA), allograft inflammatory factor 1 (AIF1), and HLA-B associated transcript 2 (BAT2). An analysis of 2,162 case-controls demonstrated the first evidence of association between a BAT2 polymorphism (rs1046089) and severe malaria.

References

  1. Ackerman HC, Ribas G, Jallow M, Mott R, Neville M, Sisay-Joof F, Pinder M, Campbell RD, Kwiatkowski DP (2003) Complex haplotypic structure of the central MHC region flanking TNF in a West African population. Genes Immun 4:476–486PubMedCrossRefGoogle Scholar
  2. Clark TG, Diakite M, Auburn S, Campino S, Fry A, Green A, Richardson A, Small K, Teo YY, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Griffiths M, Peshu N, Williams T, Marsh K, Molyneux M, Taylor T, Rockett KA, Kwiatkowski DP (2009) Tumour necrosis factor and lymphotoxin alpha polymorphisms and severe malaria in African populations. J Infect Dis (in press)Google Scholar
  3. Harney SM, Vilarino-Guell C, Adamopoulos IE, Sims AM, Lawrence RW, Cardon LR, Newton JL, Meisel C, Pointon JJ, Darke C, Athanasou N, Wordsworth BP, Brown MA (2008) Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis. Rheumatology (Oxford) 47:1761–1767CrossRefGoogle Scholar
  4. Hashimoto M, Nakamura N, Obayashi H, Kimura F, Moriwaki A, Hasegawa G, Shigeta H, Kitagawa Y, Nakano K, Kondo M, Ohta M, Nishimura M (1999) Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus. Hum Genet 105:197–199PubMedCrossRefGoogle Scholar
  5. Knight JC, Keating BJ, Kwiatkowski DP (2004) Allele-specific repression of lymphotoxin-alpha by activated B cell factor-1. Nat Genet 36:394–399PubMedCrossRefGoogle Scholar
  6. Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77:171–192PubMedCrossRefGoogle Scholar
  7. Langhorne J, Ndungu FM, Sponaas AM, Marsh K (2008) Immunity to malaria: more questions than answers. Nat Immunol 9:725–732PubMedCrossRefGoogle Scholar
  8. Malaria Genomic Epidemiology Network and Wellcome Trust Casecontrol Consortium (MalariaGEN and WTCCC) (2009) Genome-wide and fine-resolution analysis of malaria in West Africa. Nat Genet (in press)Google Scholar
  9. Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, Newton C, Winstanley P, Warn P, Peshu N et al (1995) Indicators of life-threatening malaria in African children. N Engl J Med 332:1399–1404PubMedCrossRefGoogle Scholar
  10. MHC-Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium. Nature 401:921–923CrossRefGoogle Scholar
  11. Teo YY, Fry AE, Clark TG, Tai ES, Seielstad M (2007) On the usage of HWE for identifying genotyping errors. Ann Hum Genet 71:701–703 author reply 704PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Mahamadou Diakite
    • 1
    • 2
  • Taane G. Clark
    • 1
    • 3
  • Sarah Auburn
    • 3
  • Susana Campino
    • 3
  • Andrew E. Fry
    • 1
  • Angela Green
    • 1
  • Andrew P. Morris
    • 1
  • Anna Richardson
    • 1
  • Muminatou Jallow
    • 4
  • Fatou Sisay-Joof
    • 4
  • Margaret Pinder
    • 4
  • Dominic P. Kwiatkowski
    • 1
    • 3
  • Kirk A. Rockett
    • 1
  1. 1.Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
  2. 2.Malaria Research and Training Centre, Faculty of Medicine, Pharmacy and OdontostomatologyUniversity of BamakoBamakoMali
  3. 3.Wellcome Trust Sanger Institute, Wellcome Trust Genome CampusHinxtonUK
  4. 4.Medical Research Council LaboratoriesBanjulGambia

Personalised recommendations