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

Abstract

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.

Functional polymorphisms of the TLR7 and TLR8 genes contribute to Mycobacterium tuberculosis infection

“…TLR8 is primarily expressed in monocytes/macrophages and myeloid dendritic cells [15,33]. Earlier studies have revealed the association of variant genotypes of the TLR8 polymorphisms with TB susceptibility [19,34]. Davila et al first reported that TLR8 SNPs are significantly associated with pulmonary TB among Indonesian and Russian males [19].…”

“…Davila et al first reported that TLR8 SNPs are significantly associated with pulmonary TB among Indonesian and Russian males [19]. Another study, in Turkish children [34], also showed that TLR8 polymorphisms are associated with susceptibility to pulmonary TB among males, but the mechanisms by which TLR8 recognizes MTB and intracellular signaling occurs remain M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 13 unknown. In addition, a recent genome-wide association study (GWAS) of South African Coloured (SAC) population failed to replicate previously identified polymorphisms in the TLR8 gene in Tuberculosis risk [35].…”

Diagnostic values of microRNA-31 in peripheral blood mononuclear cells for pediatric pulmonary tuberculosis in Chinese patients

“…Furthermore, new TB cases are occurring at an alarming rate of 9 million per year, with approximately 1.5 million TB-related deaths per year worldwide. While MtB poses significant risk to human health, fortunately, only 5-10% of those infected develop the active form of the disease (Dalgic et al, 2011). According to the World Health Organization (WHO) estimates, one million children develop TB worldwide, accounting for 11% of total annual TB cases (Dalgic et al, 2011).…”

“…While MtB poses significant risk to human health, fortunately, only 5-10% of those infected develop the active form of the disease (Dalgic et al, 2011). According to the World Health Organization (WHO) estimates, one million children develop TB worldwide, accounting for 11% of total annual TB cases (Dalgic et al, 2011). In 2011, half a million children (0-14 years) developed TB, and 64,000 children died from the disease.…”

Polymorphism of X-linked CD40 ligand gene associated with pulmonary tuberculosis in the Han Chinese population

“…8 TLR8 polymorphisms have been shown to be associated with TB susceptibility in Indonesian, Russian and Turkish study groups. 13,14 Four studied single-nucleotide polymorphisms (SNPs) on TLR8 were in perfect linkage disequilibrium, from which one missense 1 variant (rs3764880) was identified as the functional polymorphism causing the strong observed association with TB. When men and women were evaluated separately, an association of the rs3764880A with TB susceptibility was observed, whose effect, however, applied only to men.…”