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Variation in the ICAM1 gene is not associated with severe malaria phenotypes

A E Fry1, S Auburn, M Diakite

  • 1The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, UK. afry@well.ox.ac.uk

Genes and Immunity
|June 6, 2008
PubMed

Insights

Genetic variations in the ICAM1 gene do not appear to influence susceptibility to severe malaria. This study found no association between ICAM-1(Kilifi) polymorphisms and severe or cerebral malaria phenotypes.

Area of Science:

  • Genetics
  • Immunology
  • Infectious Diseases

Background:

  • Adhesion of Plasmodium falciparum-infected erythrocytes to intercellular adhesion molecule (ICAM)-1 is implicated in severe malaria pathogenesis.
  • Previous genetic association studies on ICAM1 polymorphisms and severe malaria susceptibility have yielded inconsistent results.

Purpose of the Study:

  • To investigate the association between ICAM1 gene polymorphisms and severe malaria phenotypes.
  • To clarify the role of ICAM-1(Kilifi) in severe malaria susceptibility.

Main Methods:

  • Genetic association studies were conducted using 15 single nucleotide polymorphisms (SNPs) around the ICAM1 locus.
  • Studies included a family-based analysis of 1071 trios from The Gambia, Malawi, and Kenya, and an additional analysis of 708 Gambian trios and 4058 individuals in a case-control study.
  • Two key non-synonymous SNPs, rs5491 (ICAM-1(Kilifi)) and rs5498 (K469E), were specifically examined.

Main Results:

  • No significant association was found between any of the studied ICAM1 polymorphisms and severe malaria phenotypes.
  • Pooled analysis for ICAM-1(Kilifi) showed no increased odds of severe malaria (OR 1.02, P=0.54) or cerebral malaria (OR 1.07, P=0.17).

Conclusions:

  • The studied ICAM1 gene polymorphisms, including ICAM-1(Kilifi), are not associated with susceptibility to severe malaria.
  • Further investigation into epidemiological, population genetic, and functional data is needed to fully understand the link between ICAM-1(Kilifi) and severe malaria.

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