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Related Experiment Videos

CD40L association with protection from severe malaria.

P Sabeti1, S Usen, S Farhadian

  • 1Wellcome Trust Centre for Human Genetics, Oxford, UK.

Genes and Immunity
|July 26, 2002
PubMed
Summary

Common variants in CD40 ligand (CD40L) were investigated for their role in severe malaria susceptibility. A specific CD40L variant was associated with a reduced risk of severe malaria in males.

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Area of Science:

  • Immunogenetics
  • Infectious Disease Epidemiology

Background:

  • CD40 ligand (CD40L) is crucial for immune responses to infection.
  • While rare CD40L mutations cause immunodeficiency, common variants' roles in disease susceptibility are unexplored.

Purpose of the Study:

  • To identify common polymorphisms in the CD40L gene.
  • To investigate the association between CD40L variants and susceptibility to severe malaria.

Main Methods:

  • Sequencing of the CD40L 5' flanking region and first exon.
  • Genotyping of identified polymorphisms in a Gambian population cohort (957 individuals).
  • Transmission Disequilibrium Test (TDT) on 371 cases with parental DNA.

Main Results:

  • Two CD40L polymorphisms were identified, with lower diversity than expected for the X chromosome.

Related Experiment Videos

  • A significant reduction in severe malaria risk (OR=0.52, P=0.002) was observed in males hemizygous for the CD40L-726C variant.
  • TDT confirmed the association was not due to population stratification (P=0.04).

    • Conclusions:

    • A common CD40L variant is preliminarily associated with malaria resistance.
    • Further genetic studies are warranted to elucidate CD40L's role in infectious diseases.