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.

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Metallothionein affects the metabolism, transport and storage of micronutrients such as zinc, copper and iron, and the detoxification of heavy metals, especially cadmium. Cd is a common, highly toxic environmental pollutant that accumulates in human placenta, elevated concentrations of which are associated with impaired zinc transfer to the fetus. This prospective study investigated the effects of metallothionein 2A (MT2A) -5 A/G single nucleotide polymorphism on the accumulation of Cd in human placenta and micronutrient transfer to the fetus in 95 pregnant women and their newborns. Venous blood from the mother was collected to investigate Cd, Zn, Cu, Fe levels and MT2A polymorphism. Cord blood from the neonate and placenta was collected for metal levels. MT2A polymorphism was determined by the standard PCR-restriction fragment length polymorphism technique. Metal levels were analyzed by Atomic Absorption Spectrometry (AAS). Maternal blood Cd levels were statistically higher for mothers with a heterozygote genotype compared with a homozygote genotype (P<0.05). In contrast, placental Cd levels were significantly higher in mothers with a homozygote rather than a heterozygote genotype (P<0.05). No difference existed in cord blood Cd, Zn and Cu levels. However, cord blood Fe levels of newborns with heterozygote genotype mothers were higher than in others. Placental Cd levels of heterozygote genotype mothers were negatively associated with Zn in cord blood. Cd exposure at environmental levels may be associated with alteration of the umbilical cord micronutrient levels for newborns with mothers of a heterozygote genotype.

This study suggests that pregnant women with AG genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level cord blood lead variation.

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The P2X7 gene polymorphisms have been linked to increased risk for pulmonary and extrapulmonary tuberculosis in some populations. In this study, the genotype and allelic frequencies 1513A-->C variant within the P2X7 gene was significantly higher than in the healthy controls (P = 0.035, P = 0.041). This is the first study demonstrating that the 1513A-->C polymorphism is associated with extrapulmonary tuberculosis in children.

The present article is the first report of clinical implications of NOD2/CARD15 gene variants in children with sepsis. Our findings suggest that common polymorphisms in the NOD2/CARD15 gene may play a major role in susceptibility to sepsis and the outcome of sepsis in children.