Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis

Nazan Dalgic,Mesut Sancar,Erkan Cakir,Zeliha Kayaalti,Tulin Soylemezoglu,Deniz Tekin

doi:10.1155/2011/545972

Abstract

Objectives:Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population.Methods:The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects.Results:We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p> 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98,p= 0.007).Conclusions:Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

Highlights

One third of the world population is infected with Mycobacterium tuberculosis (MTB), the bacterium that causes tuberculosis (TB); only 5–10% of those infected will develop active disease [1]
Using blood samples of children with pulmonary TB and the control group, we tested whether there is an association between pulmonary TB and −129 G/C and Met1Val polymorphisms in the TLR8 gene
Toll-like receptors (TLRs) play an important role in the innate immune recognition of invading microorganisms, initiating adaptive immune responses

Summary

Introduction

One third of the world population is infected with Mycobacterium tuberculosis (MTB), the bacterium that causes tuberculosis (TB); only 5–10% of those infected will develop active disease [1]. The immunological mechanisms that distinguish the majority of individuals who successfully contain these organisms from the minority who develop progressive mycobacterial disease are largely unknown. Discrimination of nonself from self is achieved by numerous host proteins equipped with the ability to recognize structures, or molecular patterns, present on foreign organisms [3]. One major family of proteins, the toll-like receptors (TLRs), play an important part in the innate immune recognition of invading microorganisms, initiating sufficient immune responses. Growing amounts of data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes, N. Dalgic et al / Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis resulting in an altered susceptibility to, or course of, infectious or inflammatory disease [4]

Objectives

Results

Conclusion