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Published on: December 4, 2015
Toll-like receptor polymorphisms in malaria-endemic populations
Jennifer A Greene1, Ann M Moormann, John Vulule
1Center for Global Health and Diseases, Case Western Reserve University, Cleveland OH, USA. jag40@cwru.edu
Malaria Journal
|March 26, 2009
Summary
Genetic variations in Toll-like receptors (TLR) and MyD88-Adaptor Like Protein (MAL) show similar frequencies across populations with differing malaria exposure, suggesting limited selective pressure from malaria on these innate immunity genes.
Area of Science:
- Human genetics
- Immunology
- Infectious disease epidemiology
Background:
- Innate immunity pathways, including Toll-like receptors (TLR), are implicated in Plasmodium falciparum malaria pathogenesis.
- Genetic polymorphisms in these innate immunity genes may be subject to selective pressures in malaria-endemic regions.
Purpose of the Study:
- To investigate the frequencies of single nucleotide polymorphisms (SNPs) and length variations in TLR2, TLR4, TLR9, and MyD88-Adaptor Like Protein (MAL).
- To determine if malaria exposure history has exerted selective pressure on these innate immune genes in diverse human populations.
Main Methods:
- A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was employed.
- Genotyping was performed on 170 residents from Kenya (holoendemic and low transmission sites), 346 from Papua New Guinea (holoendemic), and 261 from North America.
Main Results:
- Allele frequencies for TLR2, TLR4, TLR9, and MAL polymorphisms did not significantly differ between Kenyan sites with contrasting malaria exposure histories.
- Allele frequencies for TLR9 SNPs and TLR2 5' untranslated region length polymorphisms were greater than 10% in all studied populations.
- Genotype frequencies were in Hardy-Weinberg Equilibrium in Kenyan and Papua New Guinean populations.
Conclusions:
- Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms across populations with varied malaria exposure suggest these innate immune pathways have not been strongly selected by malaria.
- Hardy-Weinberg Equilibrium and Neutral Theory suggest genetic drift, rather than strong selective pressure from malaria, has influenced allele frequencies in these populations.
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