The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study.

BACKGROUND: Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge. METHODS: Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed. RESULTS: MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004). CONCLUSIONS: Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.

Influence of MRP1 G1666A and GSTP1 Ile105Val genetic variants on the urinary and blood arsenic levels of Turkish smelter workers.

To understand the cellular mechanisms responsible for arsenic metabolism and transport pathways plays a fundamental role in order to prevent the arsenic-induced toxicity. The effect of MRP1 G1666A and GSTP1 Ile105Val polymorphisms on blood and urinary arsenic levels were determined in 95 Turkish smelter workers. Blood and urinary arsenic concentrations were measured by GF-AAS with Zeeman correction and gene polymorphisms were investigated by PCR-RFLP method. The mean blood and urinary arsenic levels were 21.60±12.28µg/L and 5.58±4.37µg/L, respectively. A significant association between MRP1 1666A allele and urinary arsenic levels was found (p=0.001). GSTP1 Ile105Val polymorphism was detected not to be associated with either blood or urinary arsenic levels (p=0.384, p=0.440, respectively). Significant association was also detected between MRP1A(-)/GSTP1Val(-) genotypes and urinary arsenic levels (p=0.001). This study suggested that MRP1 G1666A alone and, also, combined with GSTP1 Ile105Val were associated with inter-individual variations in urinary arsenic levels, but not with blood arsenic levels.

Does maternal MDR1 C1236T polymorphism have an effect on placental arsenic levels?

To detect whether maternal MDR1 C1236T polymorphism has an effect on placental arsenic levels, 112 mother-placenta pairs were examined. Venous blood samples from mothers were collected to investigate the C1236T polymorphism which was detected by standard PCR-RFLP technique. Placentas were collected to measure arsenic levels by GF-AAS. The MDR1 C1236T genotype frequencies of mothers were found as 30.3% homozygote typical (CC), 51.8% heterozygote (CT) and 17.9% homozygote atypical (TT). The mean placental arsenic level was 62.36±30.43 µg/kg. It was observed that the placental arsenic concentrations were higher in mothers with TT genotype than those with CC and CT genotypes, but this was not statistically significant (p=0.702). This finding was indicated that fetuses of mothers with TT genotype may be more susceptible to arsenic toxicity as compared to those of with CC and CT genotypes. We believe that this difference warrant further studies with larger study subjects.

Association between delta-aminolevulinic acid dehydratase polymorphism and placental lead levels.

Lead inhibits the delta-aminolevulinic acid dehydratase (ALAD) activity and results in neurotoxic aminolevulinic acid accumulation in the blood. During pregnancy, lead in the maternal blood can easily cross the placenta. The aim of this study was to determine whether the maternal ALAD G177C polymorphism (rs1800435) was related to the placental lead levels. The study population comprised 97 blood samples taken from mothers to investigate ALAD G177C polymorphism and their placentas to measure lead levels. ALAD G177C polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique and atomic absorption spectrometry (AAS) equipped with a graphite furnace and Zeeman background correction system was used for lead determination. The median placental lead levels for ALAD1-1, ALAD1-2 and ALAD2-2 genotypes were 7.54 µg/kg, 11.78 µg/kg and 18.53 µg/kg, respectively. Statistically significant association was found between the maternal ALAD G177C polymorphism and placental lead levels (p<0.05). This study suggested that maternal ALAD G177C polymorphism was associated with placental lead levels.

Does maternal VDR FokI single nucleotide polymorphism have an effect on lead levels of placenta, maternal and cord bloods?

INTRODUCTION: Individual susceptibility due to genetic variations appears to be an important factor in lead toxicity. As lead, ubiquitous atmospheric pollutant, behaves very similarly to calcium, gene polymorphisms in proteins involved in calcium homeostasis can affect lead toxicokinetics. Vitamin D receptor (VDR), a DNA-binding transcription factor, activates genes that encode proteins involved in calcium metabolism. Thus, the objective of this study was to determine the effect of maternal VDR FokI polymorphism on lead levels of maternal blood, placental tissue and cord blood. METHODS: The study population comprised 116 women and their respective placenta and umbilical cord. Venous blood samples were drawn from mothers to investigate both the lead levels and VDR FokI polymorphism. Cord blood samples and placentas were collected for lead levels. VDR FokI polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Lead levels were analyzed by dual atomic absorption spectrometer system. RESULTS: Genotype frequencies of VDR FokI polymorphism were 49.2% FF, 44.8% Ff and 6.0% ff. The mean lead levels of maternal blood, placenta and cord blood were 36.76 ± 13.84 µg/L, 12.84 ± 14.47 µg/kg and 25.69 ± 11.12 µg/L, respectively. Maternal blood, placental and cord blood lead levels were found significantly to be higher in mothers with f allele for the VDR FokI polymorphism (p < 0.05). DISCUSSION: The present study indicated that this polymorphism had an effect on maternal and fetal lead levels and that mothers with F allele associated with lower lead concentration may protect their respective fetus against the toxic effects of lead exposure.

Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood.

Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the association between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother-placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR-RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods.

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels.

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metal trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01 ± 81.87 ppm, 35.59 ± 17.72 ppb and 1.25 ± 0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels.

Effect of paraoxonase 1 192 Q/R polymorphism on paraoxonase and acetylcholinesterase enzyme activities in a Turkish population exposed to organophosphate.

Organophosphate (OP) compounds are the most commonly used pesticide groups and they are commercially used in the market for local and industrial purposes. Paraoxonase 1 (PON1) enzyme plays an important role in biotransformation of OP compounds, which shows toxic effects via inhibiting the acetylcholinesterase (AChE). The aim of this study was to determine the effects of PON1 gene polymorphism and its effects on PON and AChE enzyme activities in individuals who were exposed to organophosphorus insecticides due to occupational reasons, and to profile the probability of susceptibility to organophosphorus compounds. For this purpose, 54 individuals who were exposed to OPs and 54 healthy unrelated controls were studied. First, PON1 and AChE enzyme activities were measured. Second, PON1 192 Q/R polymorphism was determined by standard polymerase chain reaction-restriction fragment length polymorphism technique. When the PON1 192 Q/R polymorphism was compared with PON1 enzyme activities, statistically significant association was found in both OP-exposed and control groups (p < 0.05). PON1 192 R(+) (QR + RR genotypes) genotype carriers had higher PON1 activities than 192 R(-) (QQ) genotype carriers. On the other hand, results were statistically analyzed in terms of AChE enzyme activities and there were statistically significant differences only in the OP-exposed group (p < 0.05). The mean AChE concentration in the OP-exposed group was determined as 33.79 ± 6.84 U/g haemoglobin (Hb) for PON1 192 R(+) carriers and 30.37 ± 7.62 U/g Hb for PON1 192 R(+) carriers. As a conclusion, PON1 and AChE activities were increasing according to the genotypes found in individuals having been exposed to OPs at a chronic level; 192 R(+) > 192 R(-), respectively.

Evaluation of DNA damage using 3 comet assay parameters in workers occupationally exposed to lead.

The aim of this study was to investigate the association between DNA damage and blood lead levels in individuals occupationally exposed to lead. To evaluate this association, 61 workers exposed to lead were monitored in terms of DNA damage in blood lymphocytes. The levels of DNA damage were measured according to 3 comet assay parameters, including tail intensity (TI), tail moment (TM), and DNA tail (DNAt). A statistically significant positive correlation was found between the lead levels and TI, TM, and DNAt (p < .01). Smoking had independent effects on DNA damage. A statistically significant difference was observed between smokers and nonsmokers in regards to DNA damage parameters (p < .05). In addition, the lead and DNA damage levels in smokers were found to be significantly higher than the levels observed in nonsmoking workers (p < . 05). Our results show that exposure to lead induces genotoxic effects in peripheral lymphocytes, as measured by comet assays.

The evaluation of arsenic and cadmium levels in biological samples of cases with lung cancer.

INTRODUCTION: Chronic exposure to the toxic metals plays an important role among the causes of lung cancer beside of smoking. We aimed to evaluate the association between the histopathologic type of lung cancer and arsenic and cadmium levels in biological samples. MATERIALS AND METHODS: This study in a single center was conducted through the years 2009-2013, including 72 patients with lung cancer, within a prospective study design. Biological samples (whole blood, scalp hair, urine) of subjects obtained before the treatment, and arsenic and cadmium levels were analyzed by atomic absorption spectrophotometer. The characteristics of lung cancer cases and metal levels were compared statistically (power: 0.74). RESULTS: Fifty six (77.8%) of patients were non-small cell lung cancer (NSCLC), 16 (22.2%) were small cell lung cancer (SCLC) in 72 study subjects (7 F/65 M, mean age= 62.2 ± 8.7 years). According to TNM staging, 27 of NSCLC were stage IV, 14 of SCLC were extensive disease. In blood, scalp hair and urine samples of cases, mean arsenic levels were 23.1 ± 9.2 µg/L, 0.6 ± 0.3 µg/g and 3.6 ± 1.9 µg/L, while cadmium levels were 1.2 ± 0.8 µg/L, 0.3 ± 0.1 µg/L and 2.8 ± 1.6 µg/L, respectively. A significant negative correlation was found between blood and urine arsenic levels (r= -0.350; p= 0.025). Blood and hair cadmium levels were also significant positive correlated (r= -0.371; p= 0.017). Both of metal levels except of urine arsenic were higher in NSCLC patients than SCLC, without any statistical significance. No significance relation was found in terms of TNM staging and mortality (p> 0.05). CONCLUSION: Any difference was observed between the arsenic and cadmium levels measured in biological samples and histopathological type, staging and mortality of patients with lung cancer in this study. We thought that further studies are needed.

Association of cadmium but not arsenic levels in lung cancer tumor tissue with smoking, histopathological type and stage.

BACKGROUND: To evaluate association of lung cancer with arsenic and cadmium levels measured in tumor tissue. MATERIALS AND METHODS: Ninety-five patients with lung cancer tumor tissue obtained surgically were included in this study. Arsenic and cadmium levels were measured and levels of metals were compared among types of lung cancer and with reference to patient data. RESULTS: The histopathologic diagnoses of the 95 cases were SCC, 49, adenocarcinoma, 28, large cell, 11 and SCLC, 1. Mean tumor arsenic and cadmium levels were 149.3±129.1µg/kg and 276.3±219.3µg/kg, respectively. Cadmium levels were significantly associated with smoking (p=0.02), histopathologic type (p=0.005), and TNM staging (r=0.325; p=0.001), although arsenic was not related to any parameter (p>0.05). There was no relation between metal levels and mortality (p>0.05). CONCLUSIONS: We found a significant association between tumor cadmium levels of patients with lung cancer and smoking, histopathologic type and staging, although there was no relation with arsenic levels.

Lymphocyte DNA damage in Turkish asphalt workers detected by the comet assay.

Asphalt has a highly complex structure and it contains several organic compounds including polycyclic aromatic hydrocarbons and heterocyclic compounds. In this study, comet assay was used to detect the DNA damage in blood lymphocytes of 30 workers exposed to asphalt fumes and 30 nonexposed controls. This is the first report on Turkish asphalt workers' investigated DNA damage using the alkaline single cell gel electrophoresis (SCGE). The DNA damage was evaluated by the percentage of DNA in the comet tail (% tail DNA) for each cell. According to our results, workers exposed to asphalt fumes had higher DNA damage than the control group (p < 0.01). The present study showed that asphalt fumes caused a significant increase in DNA damage and the comet assay is a suitable method for determining DNA damage in asphalt workers.

An association between polymorphism of the NADH/NADPH oxidase p22phox (phagocyte oxidase) subunit and aging in Turkish population.

BACKGROUND AND AIMS: Aging is a complex and multifactorial process that is stimulated by a number of factors including genes and life-style. It is thought that the production of reactive oxygen species (ROS) in the face of antioxidant enzymes and molecules is related to aging and age-related diseases. NAD(P)H oxidase system is the predominant cellular source of ROS, and p22phox, the major component of that system, is essential for the activation of NAD(P)H oxidase. The aim of this study was to investigate the association between p22phox C242T single nucleotide polymorphism and aging in Turkish population. METHODS: Blood samples were collected from 332 volunteers between 18 and 95 years of age and were classified into three groups according to their ages as <65, 65-84 and ≥ 85. p22phox C242T polymorphism was genotyped by PCR-RFLP method. RESULTS: CC genotype frequency in the C242T polymorphism is higher in older group (≥ 85) than younger groups (<65 and 65-85), whereas CT + TT genotype frequency is lower in older group. When the p22phox C242T polymorphism was compared with the mean ages and age groups, statistically significant associations were found. CONCLUSIONS: We showed for the first time that human aging is significantly associated with p22phox C242T genotypes in Turkish population, being highest in CC, intermediate in CT, and lowest in TT homozygote. It is plausible to suggest that CC genotype might protect people from chronic inflammation, diseases as well as from oxidative stress and, thus, individuals with CC genotype might be more advantageous for aging as compared to those with CT + TT genotypes.

The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?

OBJECTIVES: Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. The aim of this study was to determine whether the maternal metallothionein 2A (MT2A) -5 A/G single-nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and cord blood in 91 pregnant women and their newborns. METHODS: Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR-RFLP technique was used to determine MT2A polymorphism. RESULTS: Blood lead levels of heterozygote genotype (AG) mothers were statistically higher than those of homozygote genotype (AA) (P < 0.05). Maternal lead levels were significantly associated with cord blood lead levels for pregnant women with AA genotype (P < 0.001). This association was not statistically significant for pregnant women with AG. In contrast, the mean value of cord blood lead level for newborns with mothers of AG genotype was slightly higher than others, though the difference was not significant. No significant difference existed in placenta lead levels between the groups. CONCLUSION: 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.

Importance of NOD2/CARD15 gene variants for susceptibility to and outcome of sepsis in Turkish children.

OBJECTIVE: Severe sepsis remains a leading cause of morbidity and mortality in children. Given the link to pathogenesis, polymorphisms in genes involved in infection and inflammation may influence the outcomes in patients with sepsis and septic shock. The role of mutations within the innate immunity receptor NOD2/CARD15 has recently been demonstrated as a risk factor for bacteremia and mortality in adult patients with sepsis. The aim of this study was to evaluate the role of mutations of the NOD2/CARD15 gene in pediatric patients with sepsis. DESIGN: Prospective cohort study. SETTING: A tertiary care, ten-bed, pediatric intensive care unit. PATIENTS: One hundred twenty-eight patients with sepsis admitted to the pediatric intensive care unit and healthy control group were included. INTERVENTIONS: Venous blood from the children with sepsis and healthy controls was collected to investigate common polymorphisms (Arg702Trp, Gly908Arg, Leu1007fsincC) within the NOD2/CARD15 gene. Standard polymerase chain reaction restriction fragment length polymorphism technique was used to determine NOD2/CARD15 gene polymorphism. MEASUREMENT AND MAIN RESULTS: R702W, G908R, and Leu1007fsinsC variants in the NOD2/CARD15 gene were determined as significant risk factors associated with susceptibility to sepsis (p = .025, p = .031, p = .014, respectively). Sepsis-related mortality was increased in children carrying the Leu1007fsinsC variant (p = .041). CONCLUSIONS: 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.

The effects of metallothionein 2A polymorphism on placental cadmium accumulation: Is metallothionein a modifiying factor in transfer of micronutrients to the fetus?

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.

Effects of the interleukin-6 (IL-6) polymorphism on toxic metal and trace element levels in placental tissues.

The placenta is a crucial organ of fetal origin that functions in providing nutrients to the fetus from the mother. During pregnancy, the need for essential micronutrients, such as Fe and Zn, increases due to the requirements of the growing fetus. Maternal Fe deficiency induces an increase in Cu levels and can also affect cytokine levels in the placenta. On the other hand, Cu deficiency, although not as common, can also have destructive effects on the fetus. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities, including such as immune responses, acute-phase reactions, and inflammation. The placenta produces a significant amount of IL-6 during pregnancy. The effects of the IL-6 -174 G/C single nucleotide polymorphism (SNP) on IL-6 gene transcription and on plasma cytokine levels were assessed in the present study. We investigated the association between the IL-6 -174 G/C polymorphism and trace element/toxic metal levels in placental tissues. For the purposes of this study, 95 healthy volunteers were evaluated. Presence of the IL-6 polymorphism was determined using the standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique, and metal levels were analyzed by atomic absorption spectrometry (AAS). Based on our data, there were no significant associations between the IL-6 -174 G/C polymorphism and Pb, Cd, Fe, or Zn levels in the placental tissues (p>0.05), but a statistically significant association was detected between the polymorphism and Cu levels (p=0.016). We determined that the mean Cu levels in the placental tissues from individuals with GG, GC and CC genotypes were 5.62±1.98, 6.22±3.22 and 8.00±1.32 ppm, respectively, whereas the overall mean Cu level from the placental tissues was 5.98±2.51 ppm.

Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis.

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.

The potential effect of metallothionein 2A -5A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels.

Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins. Because of their rich thiol groups, MTs bind to the biologically essential metals and perform these metals' homeostatic regulations; absorb the heavy metals and assist with their transportation and extraction. The aim of this study was to investigate the association between the metallothionein 2A (MT2A) core promoter region -5 A/G single nucleotide polymorphism (SNP) and Cd, Pb, Zn and Cu levels in the blood samples. MT2A polymorphism was determined by the standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using the 616 blood samples and the genotype frequencies were found as 86.6% homozygote typical (AA), 12.8% heterozygote (AG) and 0.6% homozygote atypical (GG). Metal levels were analyzed by dual atomic absorption spectrophotometer system and the average levels of Cd, Pb, Zn and Cu in the blood samples were 1.69±1.57 ppb, 30.62±14.13 ppb, 0.98±0.49 ppm and 1.04±0.45 ppm, respectively. As a result; highly statistically significant associations were detected between the -5 A/G core promoter region SNP in the MT2A gene and Cd, Pb and Zn levels (p=0.004, p=0.012 and p=0.002, respectively), but no association was found with Cu level (p=0.595). Individuals with the GG genotype had statistically lower Zn level and higher Cd and Pb levels in the blood samples than individuals with AA and AG genotypes. This study suggests that having the GG genotype individuals may be more sensitive for the metal toxicity and they should be more careful about protecting their health against the toxic effects of the heavy metals.

Distributions of interleukin-6 (IL-6) promoter and metallothionein 2A (MT2A) core promoter region gene polymorphisms and their associations with aging in Turkish population.

Aging is determined as the product of an interaction among genetic, environmental and lifestyle factors. As interleukin-6 (IL-6) and metallothioneins (MTs) are related to inflammation and oxidative stress response, their genes are appropriate candidate for aging, age related diseases and infections. The aim of this study was to investigate the association between the IL-6 -174 G/C promoter region and MT2A -5 A/G core promoter region single nucleotide polymorphisms (SNPs) with longevity in Turkish population. Blood samples were collected from 354 individuals between 18 and 95 years of age. Individuals were classified into four groups according to their ages as 20-40, 41-60, 61-80, >80. IL-6 and MT2A polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Mean ages of individuals with IL-6 -74 C- carriers and C+ carriers were 49.82±20.45 years and 59.82±16.82 years, respectively. For the MT2A polymorphism, mean ages were estimated as 56.18±19.50 years for G- carriers and 47.59±13.45 years for G+ carriers. As a result, when the IL-6 and MT2A polymorphisms were compared with the mean ages and age groups, statistically significant associations were found (p<0.001 and p<0.05, respectively). In conclusion, these data support that the IL-6 -174 C+ carriers and MT2A -5 G- carriers may be more advantageous for longevity.