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  • Küçük Resim
    Öğe
    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.
  • Küçük Resim
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    eNOS and XRCC4 VNTR variants contribute to formation of nicotine dependence and/or schizophrenia
    (Comenius University, 2017) Pehlivan, Sacide; Uysal, Mehmet Ali; Aydın, Pelin C.; Pehlivan, Mustafa; Nursal, Ayşe Feyda; Yavuzlar, Hazal; Kurnaz, Serdar; Sever, Ülgen; Yavuz, Ferhat K.; Uysal, Sezer; Aydın, Nazan
    BACKGROUND: This study aimed to evaluate whether VNTR variants in the Endothelial Nitric Oxide Synthase (eNOS) and the XRCC4 gene play any role in nicotine dependence (ND) and/or Schizophrenia+ND (Sch+ND) ethiopathogenesis. METHODS: Present study included 100 individuals with ND, 60 patients with Sch+ND, and 70 healthy controls. These variants were analyzed using PCR. RESULTS: The cases with ND had higher eNOS VNTR-BB genotype than the healthy control subjects (p = 0.001). eNOS-AA genotype was lower in cases with Sch+ND and ND groups compared to the controls (p = 0.001, p = 0.001, respectively). eNOS-B allele was found significantly more frequently in Sch+ND group compared to the controls (p = 0.001). eNOS-A allele was significantly lower in ND group than the controls (p = 0.001). XRCC4-ID genotype was more common in the ND group than the control group (p = 0.001) as heterozygosity disadvantage. XRCC4-DD genotype was more common in the Sch+ND group compared to the controls (p = 0.035). The frequency of XRCC4-I allele was lower in the Sch+ND group compared to the controls (p = 0.012). CONCLUSIONS: Our results showed that eNOS and XRCC4 VNTR variants might play a potential role in Sch+ND and/or ND pathophysiology.
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    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.