Hulyam Kurt

Investigation of Association Between Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism Frequency in Turkish Patients with Schizophrenia

AIM the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is of increasing interest in etiology and treatment of various neuropsychiatric disorders. The present study aimed at detecting the incidence of ACE gene I/D polymorphism in patients with schizophrenia living in the Eskisehir region (Turkey) and also at determining whether this illness could be associated to ACE gene I/D polymorphism and serum ACE concentrations. METHODS in our study, genomic DNA was studied in a total of 237 individuals, 132 of them having been diagnosed as patients with schizophrenia and 105 of them being used as control subjects. In addition, sera from 31 patients with schizophrenia and 26 healthy subjects were used to compare serum ACE concentrations. By using polymerase chain reaction, we determined the frequency of ACE gene I/D polymorphism and measured the serum ACE concentrations by ELISA. RESULTS AND CONCLUSION distribution of ACE gene I/D polymorphism and allele frequencies between the control group genotype proportions (II 19%, ID 44%, DD 37%) and the patient group (II 19%, ID 45%, DD 36%) were not significantly different. Serum ACE concentrations were 293.15 ± 23.29 ng/mL in the control group and 362.61 ± 19.96 ng/mL in the patients. It was observed that serum ACE concentrations significantly increased in patients with schizophrenia compared with those of the control group (p < 0.05). However, no significant difference could be observed according to genotypes in serum ACE concentration.

Plasminogen Activator Inhibitor Type-1 Gene 4G/5G Polymorphism in Turkish Adult Patients with Asthma

AIM This study has been performed on asthmatic patients in the Turkish population to determine the frequency of 4G/5G polymorphism genotypes of plasminogen activator inhibitor type-1 gene, and with the aim of examining the role of this polymorphism in asthma development. METHODS Genomic DNA obtained from 165 persons (98 patients with asthma and 67 healthy controls) was used in the study. DNA was multiplied with polymerase chain reaction using 4G and 5G allele-specific primers. Polymerase chain reaction products were assessed with CCD camera by being exposed to 2% agarose gel electrophoresis. Results were evaluated with chi-square test. RESULTS No statistically significant difference between the groups with respect to genotype distribution was found (p > 0.05) in the study. The 4G allele frequency was indicated as 48% and 5G allele was as 52% in patients, whereas this was 50-50% in the control group. CONCLUSION It has been established by this study that 4G/5G polymorphism genotypes of plasminogen activator inhibitor type-1 gene do not play a role in the development of asthma in the Turkish population.

Determination of the Relationship Between rs4986790 and rs4986791 Variants of TLR4 Gene and Lung Cancer

Chronic inflammation triggers DNA damage and oncogenic mutations and causes tumor formation and tumor progression. One of the important components of the inflammatory response is Toll-like receptor (TLR) family. The objective of our study is to determine the relationship between rs4986790(+896A/G) and rs4986791(+1196C/T) gene polymorphisms and lung cancer risk. PCR-RFLP technique was carried out to identify the genotypes in 100 control individuals and 160 lung cancer patients. DNA extracted from peripheral blood samples were amplified and digested with NcoI and HinfI then visualized. We did not find any difference between genotype frequencies between controls and patients (p > 0.05) in rs4986790. But a significant difference between control group and patients with lung cancer as for genotype frequencies (χ2 = 4.19, p = 0.041) in rs4986791 variants was found. Our data indicate that any correlation was not found between rs4986790 polymorphism and lung cancer, while a correlation between rs4986791 and lung cancer has been determined and found to be associated with lung cancer risk.

Dopamine D2 receptor gene −141C Insertion/Deletion polymorphism in Turkish schizophrenic patients

Schizophrenia is a chronic and neuropsychiatric disease that affects about 0.5–1% of the world’s population. An increase in dopamine and dopamine D2 receptor (DRD2) gene products has been well described in schizophrenic patients. Several groups have studied the relationship between dopaminergic hyperactivity and cellular communications have obtained discordant results. Studies searching for the relationship between the schizophrenia and DRD2 gene have gained more interest. Our objective was to determine the relationships among schizophrenic symptoms in schizophrenia subtypes and severity of symptoms in terms of DRD2 gene −141C Insertion/Deletion [Ins/Del; I/D] polymorphism by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay method. Genomic DNA was prepared from peripheral blood by using salt extraction method. After amplification of genomic DNA, PCR products were digested with BstNI restriction enzyme for the detection of DRD2 gene −141C Ins/Del polymorphism in 73 schizophrenic patients and 60 healthy control subjects. The allelic frequencies of the DRD2 gene −141C Ins/Del polymorphism in case and control groups were 79.5 and 77.5% for I allele; 20.5 and 22.5% for D allele respectively. There was no significant difference in frequencies of genotypes and alleles between the two groups. In schizophrenic and control subjects, there were no significant relationship in severity of the disease and schizophrenia types among the −141C Ins/Del genotypes and alleles.

miRNA-146a, miRNA-155 and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis.

Osteoarthritis (OA) is the most common joint disease characterized by joint pain and a progressive loss of articular cartilage. OA known as a non-inflammatory disease. Despite this the recent studies are shown synovitis and low inflammation to have a role in OA pathophysiology. The aim of this study to determine the roles of a potential therapeutic targets miRNA-146a, miRNA-155 and JNK expression levels in OA patients. Peripheral mononuclear blood cells (PBMCs) were extracted from OA patients and healthy subjects. The expression levels of miRNA-146a, miRNA-155 and JNK were quantified using by real-time PCR assay. According to study results a statistically significant increase was observed only in miRNA-155 expression level (p=0,039). However, miRNA-146a and miRNA-155 expressions increased in the progressive stages (grade 3 and grade 4) in OA patients. Our data suggests that correlation of miRNAs regulating and signal pathways can play an important role in OA pathogenesis and disease progression.

Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2 diabetes mellitus and insulin resistance

Nucleotide‐binding oligomerization domain (NOD) 1 and NOD 2 are members of the NOD‐like receptor (NLR) family and contain a caspase recruitment domain. NLRs are located in the cytosol, bind bacterial and viral ligands and play a key role in the realization of innate and adaptive immune response, inflammation, apoptosis and reactive oxygen species generation. Insulin resistance (IR) is a leading cause of type 2 diabetes mellitus (T2DM) and associated with obesity, inflammation and pro‐inflammatory responses. NOD1 and NOD2 gene variants may affect the risk of chronic inflammation, insulin resistance and T2DM by shifting the balance between pro‐ and anti‐inflammatory cytokines. The aim of our study was to determine whether the NOD1/2 gene variants might contribute to the risk of T2DM and IR.

The actions of leptin on survival and hydrogen peroxide toxicity in primary mixed glial cells of rat

Studies indicate that leptin is involved in not only energy expenditure and food intake, but also in protection against apoptosis, in inflammation and in stimulation of proliferation in many cell types. However, leptin treatment increases the oxidative stress in many cell culture studies. This contradiction evoked a question of whether leptin acts as an oxidant or antioxidant on glial cells. We investigated the effect of leptin on glial cell survival and hydrogen peroxide (H2O2)-induced toxicity in vitro. The survival rate of the cells was determined by using 3-(4,5-D-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thyazolyl blue (MTT) method. The cells obtained from the whole brain of 1–3 day-old rat were treated with 1, 10, 100 and 1000 ng/mL leptin for 24 or 72 h. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H2O2 or well known antioxidant glutathione (GSH) were applied to the cells. Malondialdehyde (MDA) levels were measured in cell lysates to which leptin was added for 24 h. The 100 and 1000 ng/mL leptin treatment for 72 h increased the glial viability by 19% and 36%, respectively. The dose of H2O2 that killed 75% of the cells was determined as 100 µM. GSH at different doses was applied as a positive control to the cells and the dose of 500 µM completely eliminated toxic effect of 100 µM H2O2. Either the pretreatment of leptin alone for 5 h or leptin combined simultaneously with H2O2 could not eliminate H2O2-caused toxicity. Furthermore, respective leptin doses did not change the glia MDA level. We suggest that leptin can increase glia survival dose dependently, but can not eliminate H2O2-induced oxidation in primary mixed glial cell culture.

The Effects of Monosodium Glutamate and Tannic Acid on Adult Rats

Background Monosodium glutamate (MSG) is a widely-used flavor enhancer and stabilizer in ready-made or packaged foods. The excessive use of MSG has been shown to increase oxidative stress in different organ systems and causes glucose metabolism disorders, obesity, and coronary diseases. Objectives In this study, the antioxidant activity of tannic acid was investigated experimentally with respect to its protective effects against overdosed MSG-induced oxidative stress in rats. The study took place in Turkey in August 2013. Methods Four groups (n = 7) of three- to four-month-old Sprague-Dawley female rats were used in this study. The first group was the control, who were administered saline. The second group received tannic acid (50 mg/kg, 3 days) intraperitoneally (i.p.). The third group received MSG (2 g/kg, 7 days) i.p., and the fourth group received both tannic acid (50 mg/kg, 3 days, pretreatment) and MSG (2 g/kg, 7 days) i.p. The animals were euthanized ten days later. Blood was collected for determining the hematological values and blood glucose levels. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined in the brain, liver, and kidney homogenates, and in the erythrocyte hemolysate. Histopathological examination of the brain, liver, and kidneys was conducted through hematoxylin-eosin staining. Results The data showed that the tannic acid treatment statistically decreased the MDA levels in the brain tissues of the group administered MSG and tannic acid (P < 0.001) when compared to the corresponding values of the control group. The SOD activities in the blood hemolysates of the MSG and tannic acid group increased when compared to the corresponding values for the MSG group (P < 0.01). Additionally, we found that pretreatment with tannic acid reduced blood glucose levels in comparison to the levels of the MSG group (P = 0.029). The results of our study show that tannic acid pretreatment in adult rats decreased blood glucose levels and oxidative stress. Conclusions In the literature, it was observed that short-term MSG exposure does not cause significant histological changes in the kidneys, liver, or brain cortex. These findings should be re-evaluated in additional long-term studies.

Lack of Association Between Type 2 Diabetes and the 3673G / A and 9041G / A Gene Variants of Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1)

The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is expressed in many tissue types, and encodes the VKORC1 protein, which is a key enzyme in the vitamin K cycle. Although researchers have focused on the effects of vitamin K on glucose metabolism, and on its role in the development of type 2 diabetes (T2DM), no consensus has yet been reached. Therefore, here we aimed to investigate the association between VKORC1 variants and the risk of T2DM. The 3673G / A (rs9923231) and 9041G / A (rs7294) VKORC1 variants were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 control individuals and 100 patients with T2DM. The genomic regions were amplified by PCR; amplicons were digested using the AciI and NciI enzymes and visualized by agarose gel electrophoresis. The genotype frequencies of the 3673G / A variants were GG (22%), GA (56%), and AA (22%) in the control group and GG (19%), GA (52%), and AA (29%) in patients with T2DM (p > 0.05). The genotype frequencies of the 9041G / A variants were GG (37%), GA (53%), and AA (10%) in the control group and GG (46%), GA (45%), and AA (9%) in patients with T2DM (p > 0.05). In conclusion, we found no significant correlation between the control group and patients with T2DM, with regard to the different genetic models of the 3673G / A and 9041G / A variants. These data suggest that these VKORC1 gene variants may not be linked to T2DM.

A study of the possible association of plasminogen activator inhibitor type 1 4G/5G insertion/deletion polymorphism with susceptibility to schizophrenia and in its subtypes.

Inhibition of the fibrinolytic system may occur at the level of plasminogen activation, mainly by PAI‐1. Mental and physical stress caused to alterations of platelet function, and also decreased to fibrinolytic activity. Furthermore, stress‐induced thrombosis regulation was proposed to be by PAI‐1 in schizophrenia patients. In this study, the distribution of genotypes and frequency of alleles of the plasminogen activator inhibitor type 1 (PAI‐1) gene 4G/5G polymorphism in different Turkish clinical schizophrenia subtypes was investigated for its role in schizophrenia development.