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    Association of Myeloperoxidase Gene Functional Variant with Schizophrenia and Smoking in a Turkish Population
    (2020) Pehlivan, Sacide; Çetinay, Pınar; Uysal, M. Atilla; Nursal, Ayşe Feyda; Kurnaz, Selin; Sever, Ulgen; Pehlivan, Mustafa
    Objective: Etiopathogenesis of schizophrenia (SCZ) involves several risk genes that induce inflammation, environmental stress factors and changes in the innate immune system. Patients with SCZ have the highest rate of cigarette smoking and severe nicotine dependence. Myeloperoxidase (MPO), a member of subfamily of peroxidases, is most abundantly expressed in immune cells. The aim of this study was to investigate the relationship between the MPO rs2333227 variant and SCZ/smoking etiopathogenesis. Method: The study included 54 patients with SCZ, 94 smokers and 92 healthy controls. MPO rs2333227 variant was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated using the ?2 test. Results: G/G and G/A genotypes of MPO rs2333227 were detected in our study samples. The frequencies of the G/G and G/A genotypes were 53.7%, 46.3%; 56.3%; 43.7%; 68.9%, 31.1% in SCZ patients, smokers, and the control group, respectively. The allele frequencies were G: 76.9% (SCZ patients), 77.4% (smokers) 83.7% (controls); A: 23.1% (SCZ patients), 22.6% (smokers), and 16.3% (controls). There was no significant difference between the SCZ patients, smokers and controls regarding MPO rs2333227 variant either in terms of allele frequency or genotype frequency. Then we genotyped the groups as women and men. MPO rs2333227 variant genotype distribution did not differ between men and women (p>0.05). Conclusion: This study does not support the role of MPO rs2333227 variant in increasing genetic risk for SCZ/smoking in Turkish population.
  • Küçük Resim
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    Association of XRCC1 and XPD functional gene variants with nicotine dependence and/or schizophrenia: a case-control study and in silico analysis
    (Taylor and Francis Ltd., 2019) Pehlivan, Sacide; Aydın, Nizamettin; Nursal, Ayşe Feyda; Uysal, Mehmet Atilla; Pehlivan, Mustafa; Tekcan, Akın; Yavuz, Fatih Kasım; Sever, Ülgen; Yavuzlar, Hazal; Kurnaz, Selin; Uysal, Seda; Çetinay Aydın, Pınar
    OBJECTIVE: The role of DNA repair mechanisms has received attention recently in schizophrenia (Sch). Sch patients show an increased prevalence of nicotine dependence (ND). This study aimed to find out whether functional SNP variants in the XRCC1 and the XPD play any role both in ND and Sch + ND etiopathogenesis in a Turkish population which was followed up with an in silico analysis approach. METHODS:XRCC1 rs25487 and XPD rs13181 variants were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the prediction of pathogenic effect of rs25487 and rs13181 SNPs, the PANTHER and SNPs&GO programs were used. Also, the protein–protein interaction analysis was performed to retrieve functional partners of the XRCC1 and XPD protein. RESULTS:XRRC1 rs25487 GG genotype was significantly lower in both ND and Sch + ND groups than the controls (p =.001, p =.006) while G allele was lower only in Sch + ND group comparison to controls (p =.034). XPD rs13181 Lys/Lys genotype was more lower in both Sch + ND and ND groups than in controls (p =.007; p =.001). XPD rs13181 Gln allele was lower in Sch + ND group compared to controls while Lys allele was higher in ND group than controls, respectively (p =.034; p =.008). The results of in silico prediction analysis showed that the rs25487 had neutral effect while the rs13181 had a disease-related effect. CONCLUSIONS: The results of the current study revealed a possible genetic association between XRCC1/XPD variants and both in ND and Sch + ND. We think that analysis of this missense SNPs using bioinformatics methods would help diagnosis of XRCC1 and XPD-related diseases. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
  • [ X ]
    Öğe
    CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population
    (Taylor & Francis Ltd, 2019) Kurnaz, Selin; Yazici, Ahmet Bulent; Nursal, Ayse Feyda; Aydin, Pinar Cetinay; Atar, Ayca Ongel; Aydin, Nazan; Pehlivan, Sacide
    OBJECTIVE: Substance use disorders (SUD) are among the most important public health problems throughout the world. We investigated whether COMT (Val108/158Met), CNR2 (rs2501432 and rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants were associated with SUD and its clinical parameters in a Turkish population. METHODS: We conducted a case-control study among 136 subjects with SUD and 100 healthy controls. Six variants were analysed by the PCR-RFLP method. RESULTS: The CNR2 rs2229579 T/T genotype and T allele increased in SUD groups than controls while the C/C genotype and C allele were more prevalent in the control group compared to the SUD group (p = 0.000 and p = 0.001, respectively). The COMT Val108/158Met Val/Val genotype and Val allele were significantly associated with polysubstance abuse (p < 0.05). There was no significant difference between the SUD group and control group regarding genotype and allele frequencies of COMT (Val108/158Met), CNR2 (rs2501432), UCP2 (rs659366) and IL-17 (rs763780) variants. CONCLUSIONS: This is the first study that discussed the relation of these variants and SUD patients in the Turkish population. The results of the analysis indicated that the CNR2 rs2229579 variant has an effect on susceptibility to SUD, suggesting that this variant might play a role in the physiopathology of SUD. The COMT Val108/158Met variant might be an important factor affecting polysubstance use.
  • [ X ]
    Öğe
    Effect of the IL-17F rs763780 Variant on Chronic Lymphocytic Leukemia and Multiple Myeloma Risk in a Turkish Cohort
    (2018) Nursal, Ayşe Feyda; Pehlivan, Mustafa; Kurnaz, Selin; Pehlivan, Sacide
    Introduction: Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in developed countries. Multiple myeloma (MM), a clonal plasma cell disease, is the second most prevalent hematological cancer. Interleukin-17 (IL-17) can facilitate the secretion of numerous proinflammatory cytokines. The goal of the present study was to evalu-ate the effect of IL-17F rs763780 on CLL/MM susceptibility in a Turkish cohort. Methods: The study included 37 patients with CLL, 21 patients with MM, and 100 healthy controls. The IL-17F rs763780 variant was genoty-ped using polymerase chain reaction-restriction fragment length poly-morphism (PCR-RFLP). The frequencies of the alleles and genotypes in patient and control groups were compared by the ?2 test. Results: No significant difference was found in the distribution of ge-notypes and alleles frequencies for IL-17F rs 763780 between the pati-ents and the healthy controls (P>0.05).Conclusion: Our results suggest that IL-17 rs763780 variant may not contribute to CLL and MM pathogenesis.
  • Küçük Resim
    Öğe
    Possible association between DNA repair gene variants and cannabis dependence in a Turkish cohort: a pilot study
    (Taylor and Francis Ltd., 2018) Pehlivan, Sacide; Yazıcı, Ahmet Bülent; Aydın, Nazan; Nursal, Ayşe Feyda; Kurnaz, Selin; Öngel Atar, Ayça; Sever, Ülgen; Kıncır, Zeliha; Pehlivan, Mustafa; Çetinay Aydın, Pınar
    OBJECTIVE: Substance use disorder (SUD) has important effects on health and well-being. It is well known that genetic factors play a role in SUD. The purpose of this research was to investigate whether functional variants of DNA repair genes might be a risk factor for cannabis and/or synthetic cannabis dependence in a Turkish cohort. METHODS: In total, 131 patients with cannabis and/or synthetic dependence and 70 healthy controls were included in this case–control study. XRCC1 codon 399 (rs25487) and XRCC4 G1394 T (rs6869366), and XPD (rs13181) variants were determined by the polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: The XRCC1 rs25487 GG genotype and G allele were significantly lower in patients compared to controls (p = 0.005; p = 0.002, respectively). XRCC4 rs6869366 TT genotype and T allele were more common in patients compared to controls (p = 0.001, p = 0.001, respectively). It was found that patients with XPD rs13181 Lys/Gln had a significantly higher risk of cannabis dependence than control did (p = 0.00). The subjects carried XPD rs13181 Gln/Gln genotype had a 2.2-fold increased risk for cannabis dependence (p = 0.010). CONCLUSIONS: We demonstrated for the first time that DNA repair gene variants may alter individual vulnerability for SUD. This observation could be of further interest to researchers, as it could suggest new candidate genes, presumably crucial for the etiopathogenesis of the cannabis and/or synthetic cannabis dependence. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
  • Küçük Resim
    Öğe
    XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia
    (Universidade de Sao Paulo, 2018) Pehlivan, Sacide; Uysal, Metin Atilla; Aydın, Nazan; Nursal, Ayşe Feyda; Pehlivan, Mustafa; Yavuzlar, Hazal; Sever, Ülgen; Kurnaz, Selin; Yavuz, Fatih Kasım; Uysal, Suna; Çetinay Aydın, Pınar
    Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population. © 2018, Universidade de Sao Paulo. All rights reserved.