Serdal Arslan

Determination of chemical profile, antioxidant, DNA damage protection and antiamoebic activities of Teucrium polium and Stachys iberica

This work deals with the evaluation of in vitro antioxidant, DNA preventing and antiamoebic activities of the water extracts of Teucrium polium and Stachys iberica. In all systems, T. polium extract exhibited excellent activity potential than that of S. iberica. The amount of total phenolics and flavonoids were high in this extract. In the presence of 40 mg/ml T. polium extract, a significant protection was observed for native super coiled DNA of pBR322 plasmid DNA. In the presence of 32 mg/ml of T. polium extract, no trophozoite was after the 24th hour.

Myeloperoxidase G-463A polymorphism and risk of lung and prostate cancer in a Turkish population.

Myeloperoxidase (MPO) is a phase I enzyme that can bioactivate many specific procarcinogens, including polycyclic aromatic hydrocarbons and aromatic amines. The MPO gene contains a common single nucleotide polymorphism, for which the -463G>A substitution within the promoter region has been shown to reduce MPO expression and activity. We investigated the association between the MPO -463G>A polymorphism and lung and prostate cancer in a Turkish population. MPO genotypes in the study populations were determined using polymerase chain reaction-based restriction fragment length polymorphism assay. The allelic frequency was significantly different between the cases and controls for lung cancer (p=0.02), but not prostate cancer (p=0.30). No significant difference was noted between the lung and prostate cancer cases and control populations in terms of genotype distribution (p=0.07, p=0.53, respectively). Control groups of lung and prostate cancer were in Hardy-Weinberg equilibrium (p=0.87 and p=0.41, respectively). To determine the protective effect against lung cancer among individuals with the -463A allele, G/A and A/A genotypes were combined. Comparison of the G/G and G/A + A/A genotypes between the lung cancer cases and control groups showed a statistically significant relationship (p=0.032, OR=0.60, 95% CI 0.38-0.95). No gender-specific difference was found in terms of genotype distribution between the lung cancer patients and the controls (female, p=0.20; male, p=0.34). In the case of smokers, a difference in genotype distribution between the lung cancer patients and the controls was statistically significant (p=0.02), although this difference was not statistically significant for non-smokers (p=0.90). Overall, no statistically significant difference was found between the prostate cancer cases and the controls in terms of genotype combination (p=0.46, OR=0.83, 95% CI 0.51-1.36). Additionally, in smokers and non-smokers, no significant relationship was determined between the prostate cancer patients and the control population (p=0.21, p=0.91, respectively). These results suggest that the MPO -463A allele significantly contributes to a protective effect overall and in smokers against lung cancer.

An investigation of the relationship between SULT1A1 Arg213His polymorphism and lung cancer susceptibility in a Turkish population

Human sulfotransferase 1A1 (SULT1A1), the most expressed isoform of the phenol SULT1 subfamily, is an important member of sulfotransferase superfamily. A transition, G to A at position 638, in SULT1A1 gene, results in Arg213His change. This single nucleotide polymorphism reduces the activity and thermostability of SULT1A1 enzyme. Thus, in the present study the relationship between SULT1A1 Arg213His polymorphism and lung cancer was investigated. One hundred and six case and 271 control samples were studied using PCR‐RFLP. There was no significant difference in genotype and allele distribution between lung cancer and control populations (p = 0.07; p = 0.06, respectively). Compared with the SULT1A1*1/SULT1A1*1 genotype the variant SULT1A1 genotype (SULT1A1*1/SULT1A1*2 or SULT1A1*2/SULT1A1*2) was associated with a significantly increased lung cancer risk in cases (p = 0.027). In male populations, there was no significant difference between case and controls (p = 0.313). In female populations, however, this difference was found to be significant (p = 0.04). In smoker and non‐smoker populations, no significant relationship was evident between lung cancer and control population (p = 0.170, p = 0.065, respectively). Statistical analyses of histological types of lung cancer in comparison with the control individuals indicated a significant difference between SULT1A1 Arg213His polymorphism and SCC (p = 0.027) and other types of cancer (p = 0.037), except SMCC (p = 0.854). Copyright

Long non-coding RNAs in the atherosclerotic plaque

BACKGROUND AND AIMS Genetic and environmental factors are important components of the development of atherosclerosis. Long non-coding RNA (lncRNAs) have emerged as regulators of multiple pathophysiological pathways in the cardiovascular system. Here, we investigated potential associations between lncRNAs and atherosclerosis. METHODS Tissue samples from atherosclerotic coronary artery plaques and non-atherosclerotic internal mammary artery were obtained from 20 patients during coronary artery bypass surgery. Expression levels of five lncRNAs known to be associated with coronary artery disease were measured using quantitative PCR. RESULTS Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) and myocardial infarction-associated transcript (MIAT) were more expressed in the atherosclerotic arteries compared to the non-atherosclerotic arteries. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was less expressed in the atherosclerotic plaques. Expression levels of potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) and hypoxia inducible factor 1A antisense RNA 2 (aHIF) were comparable between atherosclerotic and non-atherosclerotic arteries. In the atherosclerotic plaque, expression levels of MALAT1, MIAT, KCNQ1OT1 and aHIF were inversely correlated with age. CONCLUSIONS We report significant associations between lncRNAs and atherosclerosis. These findings support a role for lncRNAs in coronary artery disease development.

Toll-like receptor 7 Gln11Leu, c.4-151A/G, and +1817G/T polymorphisms in Crimean Congo hemorrhagic fever

Crimean‐Congo hemorrhagic fever (CCHF) is a viral zoonosis. Toll‐like receptors (TLRs) initiate signaling cascades leading to the activation of the innate immune system following CCHF infection. In this study, TLR7 (Gln11Leu, c.4‐151A/G, and +1817G/T) polymorphisms were investigated in CCHF patients using polymerase chain reaction (PCR)‐based restriction fragment length polymorphism (RFLP). The study population comprised 149 CCHF patients and 171 controls. For the TLR7 Gln11Leu polymorphism, there was no significant difference between the case and control groups in allele (P = 0.144) and genotype frequencies (P = 0.219). In the TLR7 IVS1 +1817G/T polymorphism, a statistically significant difference was found in allele frequencies (P = 0.026), but there was no significant difference in the TLR7 c.4‐151A/G polymorphism (P = 0.310). There was a statistically significant difference in the distribution of the TLR7 c.4‐151GG genotypes frequencies between patients and controls (P = 0.042; OR = 2.23). Furthermore, there were statistically significant associations between the TLR7 c.4‐151A/G polymorphism and both severe disease and patient mortality (P < 0.001 and P = 0.047, respectively). The TLR7 IVS1 +1817TT genotype was also significantly associated with the case group but not the control group (P = 0.045). A strong positive linkage among TLR 7 variants was found using haplotype analysis. The incidence of two haplotypes, AGG and AGT, was determined to exhibit significant differences between the case and control groups (P < 0.001 and P < 0.001, respectively). These findings suggest that the TLR7 IVS1 +1817G/T and TLR7 c.4‐151A/G polymorphisms may be important in the susceptibility or clinical course of CCHF disease. J. Med. Virol. 87:1090–1095, 2015.

Relationship between NF-κB1 and NF-κBIA genetic polymorphisms and Crimean-Congo hemorrhagic fever.

Background: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Nuclear factor (NF)-κB regulates the expression of hundreds of genes, including inflammatory and immunoregulatory, cell cycle regulating, and anti-apoptotic genes. NF-κBIA (IκBα) encodes an inhibitory version of the NF-κB proteins. Methods: This study is the first to investigate the association between NF-κB1 − 94W/D and NF-κBIA 3→UTR A→G polymorphisms and CCHF using the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Results: There was a significant difference in NF-κB1 − 94W/D genotype distribution between CCHF patients and control populations (p = 0.001). Comparison of the WW genotype with both WD and DD genotypes revealed that the difference between CCHF patients and controls was statistically significant (p = 0.043 for WD genotype, p = 0.018 for DD genotype). However, a significant deviation was found between patients with fatal CCHF and control populations (p = 0.025). The results show that patients with fatal CCHF with the DD genotype have a 4.06-times higher risk for CCHF compared to patients in the control group (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.11–14.87). A significant difference in NF-κBIA 3→UTR A→G polymorphisms was observed between CCHF patients and controls in both AA vs AG and AA vs GG (OR 2.04, p = 0.019; OR 2.01, p = 0.049, respectively). Conclusions: Our findings suggest that NF-κB1 − 94W/D and NF-κBIA 3→UTR A→G polymorphisms may be valuable predictors of the clinical course in CCHF disease.

The Role of NF‐κB1A Promoter Polymorphisms on Coronary Artery Disease Risk

Coronary artery disease (CAD), which is now regarded as a chronic inflammatory disease, is the leading cause of death worldwide. Nuclear factor (NF)‐κB is a transcription factor that plays an important role in the regulation of the immune system. NF‐κBIA is the inhibitory version of NF‐κB. This study is the first investigation of the association between CAD and NF‐κBIA‐297 C/T, ‐826 C/T, ‐881 A/G polymorphisms in a Turkish population using PCR–RFLP method. The study population comprised 201 cases with CAD and 201 healthy controls. There was no significant difference in NF‐κB1A‐297 C/T and ‐881 A/G in allele and genotype frequencies between case and control populations. The genotype frequency of NF‐κBIA‐826TT in the patients with CAD was significantly higher than that of the controls (p = 0.015, adjusted OR = 7.09, 95% CI = 1.95–25.70). The patients with CAD also had significantly higher carriage rate of NF‐κBIA‐826T allele than the controls (p = 0.03, OR = 1.43, 95% CI = 1.03–1.99). Linkage analysis indicated a close linkage among these three variants of NF‐κBIA (for case, χ2 = 85.35 and p < 0.001; for control, χ2 = 21.58 p < 0.001) and TTG, TTA and TCG haplotypes were associated with CAD (adjusted OR = 2.54, 95% CI = 0.88–7.27; p = 0.001, adjusted OR = 1.61, 95% CI: 0.64–4.02; p = 0.04, adjusted OR = 0.08, 95% CI = 0.01–0.64; p < 0.001, respectively). NF‐κBIA‐826TT genotype may be a significant risk factor and a valuable marker for the development of CAD.

Is there any relationship between Toll-like receptor 3 c.1377C/T and -7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever?

Crimean‐Congo hemorrhagic fever (CCHF) is an infectious disease that is caused by CCHF virus. A family of transmembrane receptors called as Toll‐like receptors (TLRs) selectively acts in recognizing a wide range of microbial components and endogenous molecules released by damaged tissue and have been preserved throughout evolution. TLRs initiate some signaling cascades which activate the innate immune system. Mainly four TLRs act in protection against viral infections; TLR3 is one of them. TLR3 identifies dsRNA. By producing inflammatory cytokines and type I interferons, it generates an antiviral immune response. Proper response to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes in some indviduals, and this can cause varied susceptibility to infections. In the present work, polymerase chain reaction‐based restriction fragment length polymorphism is used to analyze the frequencies of TLR3 (c.1377C/T and −7C/A) polymorphisms in 149 CCHF patients and 171 healthy adults as controls, in Cumhuriyet University, Sivas/Turkey. We also investigated the relation between these polymorphisms and severity or mortality of CCHF disease. This is the first study investigating the TLR3 SNPs in patients with CCHF. In the present study, the frequency of the TLR3 (c.1377C/T and −7A/C) genotypes in fatal and non‐fatal cases were comparable, however, the homozygous mutant (TT) genotype frequency of TLR3 c.1377C/T in CCHF patients was significantly higher than that of the healthy controls. In conclusion, presence of TLR3 c.1377 TT genotype may have a role in the susceptibility to CCHF. J. Med. Virol. 88:1690–1696, 2016.

Genetic Structure of Brown Trout ( Salmo trutta ) Populations from Turkey Based on Microsatellite Data

This present study investigated micro- and macro-geographic microsatellite DNA variations using five polymorphic microsatellite loci from 27 brown trout populations in Turkey. Average number of alleles and average observed heterozygosity were 7.4 and 0.254, respectively. Even populations from the same sea basin and river system (the so called micro-geographic regions) had unique alleles. Genetic variation among the populations from macro-geographic regions (different sea basins and river systems) was 45.78%. The mtDNA lineages of brown trout that have previously been identified by mtDNA analyses were supported by the analysis of the microsatellite DNA data in general. The Çatak population, which belongs to the Tigris lineage, was clustered together with the Euphrates populations within the Adriatic mtDNA lineage, based on microsatellite data. Both mitochondrial and microsatellite DNA analyses have made it possible to determine a secondary contact between Adriatic and Tigris lineages.

Effect of TLR10 (2322A/G, 720A/C, and 992T/A) polymorphisms on the pathogenesis of Crimean Congo hemorrhagic fever disease

Crimean Congo hemorrhagic fever (CCHF) is a tick‐borne disease caused by the Crimean Congo hemorrhagic fever virus (CCHFV). Toll‐like receptors (TLRs) are type 1 transmembrane proteins of immune cells that play a critical role in innate and adaptive immunity. The present study first time aims to investigate the relation between TLR10 gene polymorphisms (720A/C, 992T/A, and 2322A/G), severity/non‐severity, fatality/non‐fatality, and CCFH disease by using PCR‐RFLP assay in a Turkish population. TLR10 720A/C polymorphism was determined to be statistically significant both genotype and allele frequency (P = 0,011, P = 0.015, respectively). TLR10 992T/A polymorphism was found statistically significant relationships between patient and control (P = 0.026) and individual with AA genotype have approximately three times greater risk than TT genotype (OR = 2.93). There was not a significant difference in 2322A/G genotype distribution (P = 0.152). There were also statistically significant associations between both TLR10 992T/A and 2322A/G polymorphism and patient mortality (P = 0.001 and P = 0.008, respectively). We have not found statistically any linkage among TLR10 haplotype, but individual AAA and GAT haplotype have higher risk than individual AAT haplotype (OR = 3.22, OR = 1.93, respectively). Consequently, this study shows that pathogenesis of CCHF disease is associated with the TLR10 720A/C and 992T/A polymorphisms. There is a statistically significant association in fatal/non‐fatal patients with TLR10 720A/C and 992T/A. The TLR10 992AA genotype might increase and TLR10 720CC genotype might decrease susceptibility to pathogenesis of CCHF disease. TLR 10 polymorphisms may be also an important biomarker for CCHF susceptibility and fatality rate.