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Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion molecules thrombospondin and E-selectin

K Kanchan1, S S Pati2, S Mohanty2

  • 1Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology
|July 22, 2015
PubMed

Insights

Genetic variations in adhesion and immune genes influence malaria outcomes. Specific THBS1 and ESEL gene variants increase risk, while NOSII and CRP gene variants offer protection against Plasmodium falciparum malaria.

Area of Science:

  • Genetics
  • Immunology
  • Infectious Diseases

Background:

  • Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) and immune response regulation are critical to malaria's clinical outcome.
  • Understanding genetic factors influencing malaria susceptibility and severity is crucial for disease control.

Purpose of the Study:

  • To investigate the association of single nucleotide polymorphisms (SNPs) and microsatellite repeats in THBS1, ESEL, NOSII, CRP, and MBL2 genes with falciparum malaria.
  • To determine the role of these genetic variants in disease outcome in Indian populations from endemic and non-endemic regions.

Main Methods:

  • Genotyping of 23 SNPs and one microsatellite repeat in adhesion and immune regulatory genes.
  • Case-control association studies were conducted in malaria-endemic and non-endemic Indian populations.
  • Statistical analysis included relative risk and odds ratios (OR) to assess genetic associations with malaria and its severity.

Main Results:

  • A THBS1 haplotype (CCCCA) was identified as a risk factor in the endemic region (RR = 3.78).
  • An ESEL SNP (rs5368) was associated with cerebral malaria (OR = 2.23), and another ESEL SNP (rs5359) with increased disease risk in the non-endemic region (OR = 3.62).
  • Protective associations were observed for a CRP promoter SNP (CT genotype, OR = 0.29) and NOSII microsatellite alleles and haplotypes against severe malaria in both regions.

Conclusions:

  • Genetic variants in THBS1 and ESEL genes are associated with increased risk of falciparum malaria and its severe forms.
  • Variants in NOSII and CRP genes demonstrate significant protective effects against severe malaria.
  • These findings highlight the differential contribution of investigated gene variants in determining malaria outcomes in Indian populations.

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