Person: ÖZER, SIDIKA AYŞE
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ÖZER
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SIDIKA AYŞE
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Publication Metadata only Impact of glucocorticoid receptor gene (NR3C1) polymorphisms in Turkish patients with metabolic syndrome(SPRINGER, 2016) AKKİPRİK, MUSTAFA; Kaya, Z.; Caglayan, S.; Akkiprik, M.; Aral, C.; Ozisik, G.; Ozata, M.; Ozer, A.Background The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors, including insulin resistance and type-2 diabetes, abdominal obesity, dyslipidemia, hypertension and microalbuminuria. Impaired glucocorticoid receptor (GR) activity also plays an important role in the etiology of MetS. The objective of our study is to evaluate the effects of GR gene polymorphisms (BclI, N363S, TthIII1 and ER22/23EK) in Turkish patients with MetS. Materials and methods Seventy subjects with MetS and 185 healthy controls were enrolled in the study. PCR-RFLP analysis was used for genotyping. Results for each polymorphism have been verified by allele-specific oligonucleotide analysis. Results BclI GG genotype was significantly associated with an increased risk of MetS (p = 0.02). Also, only in women, the G allele carriers were significantly associated with higher C-peptide. T allele carriers of TthIII1 polymorphism were significantly associated with higher C-peptide, triglyceride, insulin and C-reactive protein (CRP, p value 0.048, 0.022, 0.005 and 0.022, respectively), and lower fasting blood glucose (FBG, p = 0.02). The combined carriers of BclI polymorphism G allele and TthIII1 polymorphism T allele were significantly associated with higher diastolic blood pressure in all patients, and lower FBG and postprandial blood glucose in only men. All the ER22/23EK polymorphisms coexisted with polymorphic variant of TthIII1 (p = 0.0058). Conclusion The presence of homozygote polymorphic variant of BclI might be good predictive markers for the disease susceptibility. The BclI and the TthIII1 polymorphism are associated with sex-specific clinical parameters. Our findings also suggest that the combination of BclI and TthIII1 polymorphisms may play a protective role in blood glucose.Publication Metadata only PIK3CA and TP53 MUTATIONS and SALL4, PTEN and PIK3R1 GENE EXPRESSION LEVELS in BREAST CANCER(WALTER DE GRUYTER GMBH, 2020) KAYA, HANDAN; Dirican, Ebubekir; Seven, Ipek Erbarut; Kaya, Handan; Ugurlu, M. Umit; Peker, Irem; Gulluoglu, Bahadir M.; Ozer, Ayse; Akkiprik, MustafaObjective: A high frequency of PI3K signalling pathway abnormalities and TP53 mutations are critical in the development and progression of breast cancer (BCa). We aimed to detect PIK3CA and TP53 mutations via an expression analysis of PIK3R1, PTEN and SALL4 and correlate the expression of these genes with clinical parameters of BCa. Materials and methods: PIK3CA and TP53 mutations in BCa samples were analysed by High-Resolution Melting (HRM) analysis, followed by Sanger sequencing, and the expression levels of PIK3R1, PTEN and SALL4 were evaluated by RT-PCR methods. Results: The frequency of PIK3CA and TP53 mutations was 42% and 38% according to the HRM and Sanger sequencing. There was a significantly high frequency of these mutations in ER(+), N0 and HER2(-) tumour samples. PIK3R1 and PTEN expression levels were high in tumour samples, whereas SALL4 expression was low. In patients with TP53 mutations, PIK3R1 expression was low, and this finding was statistically significant. PIK3R1 and PTEN expression levels showed statistically significant, respectively in G3 grades, ER(+), (PR)(+), HER2(+) and ER(+). Conclusions: We suggest that these candidate genes could be potential prognostic biomarkers of BCa and that they should be considered in the evaluation of clinical parameters of BCa.Publication Open Access Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women(WILEY, 2017-09) GÜLLÜ AMURAN, GÖKÇE; Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Amuran, Gokce Gullu; Ozmen, Tolga; Gulluoglu, Bahadir M.; Kaya, Handan; Ozer, AyseBackgroundBoth insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. MethodsTelomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. ResultsTelomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. ConclusionThese results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association.Publication Metadata only Analysis of p53 Gene Polymorphisms and Protein Over-expression in Patients with Breast Cancer(SPRINGER, 2009) KAYA, HANDAN; Akkiprik, Mustafa; Sonmez, Ozgur; Gulluoglu, Bahadir M.; Caglar, Hale B.; Kaya, Handan; Demirkalem, Pakize; Abacioglu, Ufuk; Sengoz, Meric; Sav, Aydin; Ozer, Aysep53 polymorphic variants play an important role in the determination of tumor phenotype and characteristics in breast cancer. In this study, we examined three common polymorphisms in p53 gene and their haplotype combinations to assess their potential association with inherited predisposition to breast cancer development, in relations with the protein over-expression and patients' demographic data. A total of 99 patients with breast cancer and 107 age-matched healthy controls were included in the study. Genotypes were determined using PCR-RFLP and DNA sequencing techniques. Evaluation of p53 protein overexpression was also examined by immunohistochemistry. Among three polymorphisms, increased codon 72 Pro allele frequency (p=0.0067) and the presence of Pro allele were found to be significantly associated with breast cancer (p=0.013). A significant risk was also found in subjects with combinations of specific haplotypes and genotypes. Most of breast cancer women especially younger than 50 years carry at least one p53 polymorphism (p=0.001). There was no any association between these three p53 polymorphisms and the protein over-expression, separately or in interaction, with breast cancer. In conclusion, presence of proline allele at codon 72 alone, and its special combinations with other two polymorphisms appear to be a significant risk factor for breast cancer. Determination of well-known p53 polymorphisms might be a good predictor for breast cancer development especially in women younger than 50 years.