Toll-like Receptor Polymorphisms in Malaria-endemic Populations

Overview

Journal Malar J

Publisher Biomed Central

Specialty Tropical Medicine

Date 2009 Mar 26

PMID 19317913

Citations 18

Authors

Jennifer A Greene

Ann M Moormann

John Vulule

Moses J Bockarie

Peter A Zimmerman

James W Kazura

Affiliations

Soon will be listed here.

Abstract

Background: Toll-like receptors (TLR) and related downstream signaling pathways of innate immunity have been implicated in the pathogenesis of Plasmodium falciparum malaria. Because of their potential role in malaria pathogenesis, polymorphisms in these genes may be under selective pressure in populations where this infectious disease is endemic.

Methods: A post-PCR Ligation Detection Reaction-Fluorescent Microsphere Assay (LDR-FMA) was developed to determine the frequencies of TLR2, TLR4, TLR9, MyD88-Adaptor Like Protein (MAL) single nucleotide polymorphisms (SNPs), and TLR2 length polymorphisms in 170 residents of two regions of Kenya where malaria transmission is stable and high (holoendemic) or episodic and low, 346 residents of a malaria holoendemic region of Papua New Guinea, and 261 residents of North America of self-identified ethnicity.

Results: The difference in historical malaria exposure between the two Kenyan sites has significantly increased the frequency of malaria protective alleles glucose-6-phoshpate dehydrogenase (G6PD) and Hemoglobin S (HbS) in the holoendemic site compared to the episodic transmission site. However, this study detected no such difference in the TLR2, TLR4, TLR9, and MAL allele frequencies between the two study sites. All polymorphisms were in Hardy Weinberg Equilibrium in the Kenyan and Papua New Guinean populations. TLR9 SNPs and length polymorphisms within the TLR2 5' untranslated region were the only mutant alleles present at a frequency greater than 10% in all populations.

Conclusion: Similar frequencies of TLR2, TLR4, TLR9, and MAL genetic polymorphisms in populations with different histories of malaria exposure suggest that these innate immune pathways have not been under strong selective pressure by malaria. Genotype frequencies are consistent with Hardy-Weinberg Equilibrium and the Neutral Theory, suggesting that genetic drift has influenced allele frequencies to a greater extent than selective pressure from malaria or any other infectious agents in these populations.

Citing Articles

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Network-driven analysis of human-Plasmodium falciparum interactome: processes for malaria drug discovery and extracting in silico targets.

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A preliminary assessment of and gene polymorphisms in Papua New Guinea - what does it mean for HIV/AIDS?.

Willie B, Gare J, King C, Zimmerman P, Mehlotra R P N G Med J. 2018; 60(1-2):51-59.

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