A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in

G A Awandare1, C Ouma, C C Keller

  • 1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Genes and Immunity
|August 25, 2006
PubMed

Insights

Genetic variations in the macrophage migration inhibitory factor (MIF) gene influence malaria outcomes. The MIF -173CC genotype increases the risk of high-density parasitemia (HDP) in Kenyan children.

Area of Science:

  • Immunogenetics
  • Molecular Epidemiology
  • Infectious Diseases

Background:

  • Macrophage migration inhibitory factor (MIF) is a key cytokine regulating immune responses.
  • Functional promoter variants in the MIF gene are linked to inflammatory diseases.
  • The impact of MIF genetic variation on malaria susceptibility is understudied.

Purpose of the Study:

  • To investigate the association between MIF -173 genetic variants and malaria disease outcomes in Kenyan children.
  • To explore the relationship between MIF gene variability and susceptibility to high-density parasitemia (HDP) and severe malarial anemia (SMA).

Main Methods:

  • A study involving 477 Kenyan children (aged 3-36 months) in a holoendemic malaria region.
  • Genotyping for the MIF -173 G to C transition.
  • Multivariate analysis controlling for age, gender, HIV-1 status, and sickle-cell trait.

Main Results:

  • The MIF -173CC genotype was associated with an increased risk of HDP compared to the MIF -173GG genotype.
  • No significant association was found between MIF -173 variants and SMA susceptibility.
  • Homozygous G alleles correlated with lower basal MIF levels, while hemozoin stimulation altered MIF production differently between GG and GC genotypes.

Conclusions:

  • MIF gene variability at the -173 position influences MIF production.
  • MIF -173 genetic variants are associated with susceptibility to high-density parasitemia in children with malaria.