Vitamin-D Binding Protein Gene Polymorphisms and Serum 25-Hydroxyvitamin-D in a Turkish Population.

The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s/2 (35.3%) and Gc1s/1s (31.4%), and Gc1f/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19.

Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer.

METHODS: In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. RESULTS: We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. CONCLUSIONS: Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.

Anesthesia may alter mRNA expression of certain wound healing-associated genes in dermal wound environment of the rats.

Some anesthetics including ketamine/xylazine and thiopental have been shown to alter the expression of genes related with inflammatory cytokines and chemokines in previous studies unassociated with wound healing, arising the question of whether commonly used anesthetics in wound healing models could interfere with the transcriptional responses of the genes associated with skin wound healing. The gene expression profile in wound biopsies of rats who received widely used anesthetics doses of intraperitoneal ketamine/xylazine (50 mg/kg and 10 mg/kg) or thiopental (50 mg/kg) in comparison with control rats was analyzed by monitoring the expression of genes effective on various phases of wound healing. The expression levels of 84 genes were determined on 3rd, 7th and 14th days of post-wounding using a qPCR array system. Of the genes either up or downregulated fivefolds or more, three (Egf, Col5a1 and Cxcl3) and two (Tgfa and Il2) genes were found to be the most responsive ones to ketamine/xylazine or thiopental anesthesia respectively in a period of 14 days after correction for multiple testing. However, up to 22 and 24 genes for ketamine/xylazine and thiopental were found to be differentially expressed in the same period without correction for multiple-comparisons testing (p < 0.05). In conclusion, our data suggest that ketamine/xylazine and thiopental may alter the transcriptional responses of some genes associated with wound healing in rats. We strongly suggest to consider the possible alteration effect of these anesthetics on gene expression in animal models of dermal wound healing.

Investigation of poly (ADP-ribose) polymerase-1 genetic variants as a possible risk for allergic rhinitis.

Recent studies point toward the involvement of poly (ADP-ribose) polymerase-1 (PARP-1) in the pathogenesis of allergic airway inflammation, such as asthma and allergic rhinitis (AR). It has been suggested that inhibition of PARP-1 provides significant protection against systemic or tissue inflammation in animal models. The objective of this study was to investigate whether single-nucleotide polymorphisms of PARP-1 gene are associated with genetic susceptibility to AR. We studied the effect of promoter variations and Val762Ala polymorphism of the PARP-1 gene on the risk for developing AR in a case-control association study with 110 RA patients and 130 control subjects in a Turkish population. The polymorphisms of 410 C/T, -1672G/A, and Val762Ala in the PARP-1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Haplotype analysis of these groups was also performed. The results were statistically analyzed by calculating the odds ratio (OR) and their 95% confidence intervals using χ(2) tests. The heterozygote genotype of the promoter polymorphism (-1672) was significantly found to be associated with susceptibility to AR (OR: 0.56) among the tested single-nucleotide polymorphisms. Haplotypes of PARP-1 -410, -1672, and 762 were not associated with an increased risk for AR. These results raise the possibility that the promoter (-1672) polymorphism of the PARP-1 gene may be a risk factor for AR.

LKB1 downregulation may be independent of promoter methylation or FOXO3 expression in head and neck cancer.

The serine/threonine kinase liver kinase B 1 (LKB1) is a multifunctional protein and has been associated with various cancer types. Although the tumor suppressor function of LKB1 is attributed mainly to its ability to phosphorylate directly different adenosine monophosphate-activated protein kinases, its regulation is still poorly understood. More recently, it has been shown that LKB1 expression can be regulated by forkhead box O transcription factors via cis-acting elements, which are found in the promoter region of the LKB1 gene. In this study, we investigated LKB1 messenger RNA expression levels in association with the promoter methylation of the gene and forkhead box O member 3 (FOXO3) messenger RNA expression in head and neck squamous cell carcinoma (HNSCC) tumor samples. Our results show that LKB1 expression is downregulated, especially in advanced-stage tumor samples, and this downregulation was not the result of promoter methylation or modulation by FOXO3 (P = 0.656). Despite observing a positive association between the LKB1 and FOXO3 expression levels in the tumors, this association was not statistically significant (P = 0.24). Our results indicate that downregulation of LKB1 is independent of FOXO3 and may be implicated in the progression of HNSCC.

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency.

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 +/- 1.9 vs 5.0 +/- 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.

Polymorphisms of DNA repair genes XPD and XRCC1 and risk of cataract development.

The association between oxidative or ultraviolet (UV) light induced DNA damage in the lens epithelium and the development of lens opacities, and the existence of DNA repair in lens epithelial cells have been reported. Polymorphisms of DNA repair enzymes may affect repair efficiency. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD) codon 751 and X-ray cross-complementing group 1 (XRCC1) codon 399, in a sample of Turkish patients with maturity onset cataract. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we analysed XRCC1-Arg399Gln and XPD-Lys751Gln polymorphisms in 195 patients with cataract (75 patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30 with mixed type) and in 194 otherwise healthy control group of similar age. There was a significant difference between frequencies for XPD-751 Gln/Gln genotype in cataract patients (12%) and healthy controls (20%) (P=0.008, OR=0.40, 95% CI=0.20-0.81). After stratification by the cataract subtypes, XPD-751 Gln/Gln genotype was found to be significantly different in patients with cortical (4%) type cataract in respect to control subjects (20%) (P=0.038, OR=0.16, 95% CI=0.04-0.64). In addition, the allele frequency of the C (Gln)-allele of XPD-Lys751Gln was found to be significantly different in mixed type cataract group (P=0.008, OR=0.48, 95% CI: 0.26-0.90). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in XRCC1 gene between the groups. These findings suggest that polymorphism in XPD codon 751 may be associated with the development of maturity onset cataract.

Glutathione-S-transferase M1 and T1 genetic polymorphisms and the risk of cataract development: a study in the Turkish population.

In this study, we aimed to determine the effects of genetic polymorphisms of glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) on risk of developing different subtypes of age-related cataract in the Turkish population. Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were analyzed in 195 patients with age-related cataract (75 patients with cortical, 53 with nuclear, 37 with posterior subcapsular, and 30 with mixed type) and in 136 patients of an otherwise healthy control group of similar age. GSTM1 null genotype had a significant association with the development of cataract in female subjects (p < 0.0029; OR, 2.98; 95% CI, 1.41-6.34). This relationship in female subjects was only in nuclear and mixed types cataract cases (p < 0.002; OR, 4.58; 95% CI, 1.67-12.78 and p < 0.03, respectively). There was also a statistically significant association between the combination of GSTM1-null and GSTT1-positive genotypes and the risk of cataract development in female subjects (p = 0.01; OR = 2.87; 95% CI = 1.25-6.69). Stratification by the subtypes revealed that this association was only in nuclear type cataract (p = 0.001; OR, 3.92; 95% CI, 1.34-11.71). GSTM1-null genotype or combination of the GSTM1-null and GSTT1-positive genotypes in females may be associated with increased risk of cataract development in the Turkish population.

The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients.

Glutathione S transferases (GSTT1, GSTM1, GSTP1) are enzymes that activate the detoxification of endogenous and exogenous agents. The genetic polymorphism in these genes may change the response of individuals to environmental toxicants. The genetic polymorphisms of GSTT1, GSTM1, GSTP1 have been studied extensively in the determination of individual cancer risks. Some studies showed a strong relationship between polymorphism of GSTs and superoxidedismutase enzymes. Using the polymerase chain reaction (PCR) the prevalence of genetic polymorphisms of GSTT1, GSTM1 and MnSOD (Manganese Superoxide Dismurase) was investigated in 104 cases and controls to seek any association with the risk of bladder cancer. The frequency of GSTT1 +/+ polymorphism was 65% (33/51) in the cases and 79% (42/53) in the controls. The frequency of the GSTM1 +/+ polymorphism was 33% (17/51) in the cases and 58% (31/53) in the controls. The frequency of the GSTM1 null genotype was 42% (22/53) in the controls and 68% (34/51) in the patients. The frequency of the SOD AA genotype was 36% (17/51) in the cases and 33% (19/53) in the controls. There was no association between the GSTT1 and SOD polymorphism and bladder cancer incidence. The incidence of the GSTM1 null genotype was increased in bladder cancer patients compared to controls (OR = 1.755, 95% CI = 1.119-2.751).

Glutathione S transferase M1 and T1 genetic polymorphisms are related to the risk of primary open-angle glaucoma: a study in a Turkish population.

BACKGROUND: Genetic factors and oxidative damage have been shown to have a role in the development of primary open angle glaucoma (POAG). AIM: To determine the effects of genetic polymorphisms of glutathione S transferase (GST)M1 and GSTT1 on the risk of POAG in a Turkish population. METHODS: Using a multiplex polymerase chain reaction (PCR), GSTM1 and GSTT1 gene polymorphisms were analysed in 144 patients with POAG and in 121 otherwise healthy controls of similar age. RESULTS: The GSTM1 positive genotype and the GSTT1 null genotype had an increased risk of developing POAG (p<0.001, OR 2.93, 95% CI 1.66 to 5.20 and OR 4.25, 95% CI 2.30 to 7.80, respectively). The risk of glaucoma also increased significantly in subjects with a combination of GSTM1 positive and GSTT1 null genotypes (p<0.001, OR 3.46, 95% CI 1.64 to 7.38). CONCLUSION: The GSTM1 positive genotype and GSTT1 null genotype or the combination of both may be associated with the increased risk of development of POAG in the Turkish population.

The effects of vigabatrin on rat liver antioxidant status.

The anti-epileptic drug vigabatrin was developed as an inhibitor of gamma-aminobutyric acid transaminase, and its ability to increase inhibition in the central nervous system led to its testing in an animal model. In animal models chronic use of vigabatrin is associated with irreversible myelin vacuolation. Antioxidant drugs change the antioxidant capacity of the body. Oxidative stress of the body increased when valproic acid and carbamazepine were used chronically. To assess whether vigabatrin may affect protein oxidation and lipid peroxidation, glutathione, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were studied in the livers of 57 rat fetuses after administration of vigabatrin to the mothers (19 in the first week of pregnancy, 20 in the second week, and 18 in the third week) and in 19 control rat fetuses without vigabatrin. We compared the results of administration of vigabatrin in each group with the controls. Rat fetus protein oxidation in group I (0.686 nmol/mg protein) and group II (0.723 nmol/mg protein) was higher than in the control group (0.388 nmol/mg protein). Lipid peroxidation (0.209, 0.224, 0.253 nmol/mg protein, respectively) and GPx levels (345.4, 329.0, 283.2 nmol/mg protein, respectively) of groups I, II, and III were higher than in the control group (0.104, 167.2 nmol/mg protein, respectively). GST in group II (79.2 nmol/mg protein) and group III (77.8 nmol/mg protein) were not different from that in the control group (78 nmol/mg protein). It was found that vigabatrin affected all the parameters that were studied, especially in group I, which was given the drug in the first week of pregnancy.

Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis.

To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.