Meral Yilmaz

Association of microsomal epoxide hydrolase gene polymorphism and pre‐eclampsia in Turkish women

Aim:  To assess the association between human epoxide hydrolase exon 3 and 4 polymorphisms and pre‐eclampsia by carrying out a case‐control study in Turkish women.

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever

BackgroundAlthough there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients.MethodsIn total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis.ResultsThe mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases.ConclusionsThe increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.

Lack of Association between the MTHFR C677T Polymorphism and Lung Cancer in a Turkish Population

BACKGROUND In this case-control study, we aimed to investigate the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and lung cancer. MATERIALS AND METHODS Total 200 individuals including 100 patients with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was performed using PCR and RFLP methods. RESULTS The majority of the patients were men and 90% were smokers. We found that the risk ratio for development of LC was 13-times higher in smokers compared with non-smokers between patient and control groups in our study (OR:13.5, 95%CI:6.27-29.04, p:0.0001). Besides, the risk ratio for development of LC was nine times higher in individuals with cancer history in their family than those without cancer history (OR:9.65, 95%CI: 2.79-33.36; p:0.0001). When genotype distributions and allele frequencies were analyzed in the study groups, no significant difference was apparent (χ2:0.53, p=0.76). In addition, no correlation between genotypes of MTHFRC677T polymorphism and histological type of LC was found (χ2:0.99, p=0.60). CONCLUSIONS These results suggest that there was no association between the MTHFR C677T polymorphism and lung cancer in the Turkish population.

Relationship between IFNA1, IFNA5, IFNA10, and IFNA17 gene polymorphisms and Crimean-Congo hemorrhagic fever prognosis in a Turkish population range.

Crimean‐Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN‐alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1 ‐1823G/A (rs1332190), IFNA5 ‐2529T/A (rs758236), IFNA10 Cys20stop (rs10119910), and IFNA17 Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR‐RFLP methods. The frequency of IFNA1 ‐1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%; P = 0.01). For IFNA17 Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%; P = 0.039). The distribution of TT + TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%; P = 0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P > 0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P > 0.05). The results show that IFNA1 rs1332190 and IFNA17 rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations. J. Med. Virol. 88:1159–1167, 2016.

Significant Association Between Polymorphisms of Wnt Antagonist Genes and Lung Cancer

Abstract Further elucidation of the molecular mechanisms underlying lung cancer (LC) is essential for the development of new effective therapeutic agents. Recently, involvement of Wnt antagonists in oncogenesis has been demonstrated in several cancers. The investigation of their contribution to lung carcinogenesis is still under investigation. We aimed to investigate whether there is a susceptibility or preventive effect of Wnt antagonist gene polymorphisms on the development and/or prognosis of LC. We investigated 110 LC patients and 160 controls. Single-nucleotide polymorphisms of Wnt antagonist genes including DKK2 (rs17037102), DKK3 (rs3206824), DKK3 intron4 G/C (rs7396187), DKK4 (rs2073664), and sFRP4 (rs1802074) were analyzed using nested polymerase chain reaction and restriction fragment length polymorphism. Results showed that patients with DKK3 AA compared with controls have a decreased risk of LC (adjusted for smoking habit, body mass index, and familial history) (P = 0.02; odds ratio [OR],0.08; 95% confidence interval [95% CI], 0.01–0.7). It was found that, for sFRP4 polymorphism, patients with GG and GA genotypes versus AA genotype controls showed a decreased risk for LC (P = 0.01; [OR, 0.19; 95% CI, 0.05–0.73 for GG genotype]; [OR = 0.18, 95% CI, 0.04–0.72 for GA genotype]). In addition, a decreased risk of LC was also found for the genotype combination of DKK3 (rs3206824) GG and sFRP4 AG + GG (P = 0.004; OR, 0.12; 95% CI, 0.02–0.58). We suggest that these 2 polymorphisms have a protective effect on LC in this study.

Is there a relation between Murine double minute 2 T309G polymorphism and lung cancer risk in the Turkish population

Abstract Introduction: Association between Murine double minute 2 T309G polymorphism and lung cancer risk has been investigated in several populations, but results of these studies are inconsistent. We aimed to investigate the effect of Murine double minute 2 T309G polymorphism on development of lung cancer in a Turkish population. Methods: Total 200 subjects including 100 patients and 100 controls were analyzed and used polymerase chain reaction and restriction fragment length polymorphism methods for genotyping analysis of the polymorphism. Results: We found that smokers compared with non-smokers have approximately eight fold higher lung cancer risk [p=0.0001, OR=8.27 (4.02–16.9)]. Frequency of GG genotype was higher in patients than in controls, but this ratio was not significant (χ2=3.5, p=0.17). Genotype distribution of the polymorphism was not different neither patients with non-small cell lung cancer nor patients with small cell lung cancer (χ2=2.89, p=0.57). We analyzed together with demographic feature (except smoking habit), clinicopathological findings and genotype frequencies of this polymorphism, and any association with lung cancer risk was not obtained. Conclusion: No correlation between Murine double minute 2 T309G polymorphism and lung cancer risk was detected in this Turkish population. Özet Giriş: Çeşitli popülasyonlarda akciğer kanseri riski ile Murine double minute 2 T309G polimorfizminin birlikteliği incelenmiş, fakat bu çalışmaların sonuçları arasında tutarsızlık olduğu görülmüştür. Bu çalışmada, bir Türk popülasyonunda akciğer kanserinin gelişimi üzerine Murine double minute 2 polimorfizminin etkisini araştırmayı amaçlanmıştır. Yöntemler: Bu çalışmada, 100 hasta 100 kontrolden oluşan toplam 200 örnek incelenmiş ve bu polimorfizmin genotip analizi için polimeraz zincir reaksiyonu ve restriksiyon fragment uzunluk polimorfizmi yöntemleri kullanılmıştır. Bulgular: Çalışmada sigara içmeyenlerle karşılaştırıldığında sigara içenlerin yaklaşık olarak sekiz kat daha fazla akciğer kanseri gelişme riskine sahip oldukları bulunmuştur [p=0.0001, OR=8.27 (4.02–16.9)]. GG genotipi kontrollere oranla hastalar arasında daha yüksek oranda bulunmuştur fakat bu oran anlamlı değildir (χ2=3.5, p=0.17). Bu polimorfizmin genotip dağılımı ne küçük hücreli akciğer kanseri olan hastalarda ne de küçük hücreli olmayan akciğer kanseri olan hastalarda farklılık göstermediği bulunmuştur (χ2=2.89, p=0.57). Polimorfizmin genotip sıklıkları, klinikopatolojik bulgular ve demografik özellikler (sigara alışkanlığı hariç) birlikte değerlendirilmiş ve bu bulgular arasında akciğer kanseri riski ile herhangi bir ilişki elde edilememiştir. Sonuç: Bu Türk popülasyonunda akciğer kanseri riski ve Murine double minute 2 T309G polimorfizmi arasında bir korelasyon belirlenememiştir.

The Association of MYNN and TERC Gene Polymorphisms and Bladder Cancer in a Turkish Population

PURPOSE Researchers reported that, MYNN rs10936599 polymorphism is in strong or moderate linkage disequilibrium with SNPs within the 3q26.2 chromosomal regions that also include the TERC gene. In addition, it has been reported that MYNN rs10936599 had a strong cumulative association with bladder cancer risk, and TERC gene suppresses cell growth in bladder cancer cell lines. Therefore, we aimed to determine whether polymorphisms of MYNN rs10936599 and TERC rs2293607 play any roles for bladder cancer in the Turkish population in this study. MATERIALS AND METHODS In this case-control study, 70 patients and 150 controls were investigated. Genotyping analysis was performed by polymerase chain reaction, restriction fragment length polymorphism and DNA sequencing techniques. RESULTS Genotype distribution between study groups for MYNN rs10936599 SNP was significantly different (P = .001); although there was no difference in genotype distribution for TERC rs2293607 SNP. In addition, patients with CT genotype and CT+TT genotype combination of MYNN SNP have a decreased risk for bladder cancer. Two times increased risk ratio on development of bladder cancer was obtained for CC genotype of the SNP (P = .001). Besides, it was found that genotype combination of GG+AG/CC versus AA/CC genotypes (TERC/MYNN)showed stronger correlation. We observed that statistically significant relationship between the C-G haplotypes of two polymorphisms and bladder cancer risk (P = .0001). CONCLUSION At the end of the study, we suggested that there may exist an association between a combination of MYNN rs10936599 and TERC rs2293607 polymorphisms and development of bladder cancer in Turkish population.

Investigation of LAMTOR1 gene and protein expressions in germinal vesicle and metaphase II oocytes and embryos from 1-cell to blastocyst stage in a mouse model

Improving the success of in vitro fertilization (IVF) and infertility treatment depend on understanding basic cellular and molecular mechanisms of human preimplantation development. Pre-implantation mouse embryo model is an ideal empiric system to understand these mechanisms. This study was aimed to investigate the gene and protein expressions of LAMTOR1 in mouse oocytes and pre-implantation embryos at different developmental stages. The findings demonstrate that LAMTOR1 was detected in the oocytes and in subsequent all stages of embryo development. The expression was increased progressively from MII-stage oocyte to morula stage embryo (p < 0.05), highest expression was identified in morula stage (p < 0.05), and decreased in blastocyst stage (p < 0.05). Immunofluorescence analysis showed outer and inner nuclear membranes and cytoplasmic subcellular localizations of LAMTOR1 in oocytes and pre-implantation embryos. The LAMTOR1 immunoexpression was gradually increased from MII oocyte and the highest level was detected at the morula stage of embryo development (p < 0.05). The lowest LAMTOR1 immunoexpression was detected at GV-stage oocyte (p < 0.05) and no clear difference in M2 oocyte, I-cell, 2-cell, and blastocyst stage embryos. In conclusion, both the mRNA and protein levels of LAMTOR1 increase progressively in cleavage-stage mouse embryos. LAMTOR1 has a significant higher embryonic expression at 2-cell to morula stage. LAMTOR1 may play a role in the oogenesis process and probably required for further developmental stages and it may play a possible role in the process of compaction and cavitation in mice. Therefore, further studies are needed to explore the LAMTOR1 expression especially in the different stages of embryonal development.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population.

eNOS gene polymorphisms in paraffin-embedded tissues of prostate cancer patients.

BACKGROUND/AIM The purpose of the present study was to investigate whether endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in prostate cancer (PCa). MATERIALS AND METHODS We examined three eNOS gene polymorphisms (T-786C promoter region, G894T, and Intron 4 VNTR 4a/b) at extracted DNAs from 50 formalin-fixed paraffin-embedded tissues of PCa patients. For the controls, blood samples obtained from 50 healthy men were studied. Genotyping of molecular variants was performed by PCR-RFLP technique. RESULTS We found that the TC genotype of the T-786C polymorphism was associated with PCa risk (OR: 3.325, CI: 1.350-8.188, P = 0.008). The eNOS G894T polymorphism was also associated with PCa. The frequency of the 894T allele was significantly higher in PCa patients. No association was identified between intron 4 VNTR polymorphism and PCa. CONCLUSION We found significant differences in genotypic and allelic frequencies between PCa patients and controls for eNOS T-786C and G894T polymorphisms. The presence of the T-786C genotype and 894T allele in carriers increased the risk of PCa. No association was found between intron 4 VNTR polymorphism and PCa patients.