Person: EREN, FATİH
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EREN
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FATİH
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Publication Metadata only Preliminary evidence of an association between the functional c-kit rs6554199 polymorphism and achalasia in a Turkish population(WILEY, 2012) EREN, FATİH; Alahdab, Y. O.; Eren, F.; Giral, A.; Gunduz, F.; Kedrah, A. E.; Atug, O.; Yilmaz, Y.; Kalayci, O.; Kalayci, C.Background C-kit-positive interstitial cells of Cajal (ICC) of the lower esophageal sphincter are reduced in achalasia. Two functional gene polymorphisms (rs2237025 and rs6554199) within the c-kit gene may affect its transcriptional activity. In this pilot study, we hypothesized that these polymorphisms would be associated with achalasia. Methods Genomic DNA was extracted and real-time PCR reactions were used to determine the rs2237025 and rs6554199 c-kit polymorphisms in 88 Turkish patients with achalasia and 101 healthy controls. Key Results The frequency of the T allele of rs6554199 was significantly higher in patients with achalasia [odds ratio (OR): 1.55; 95% confidence interval (CI), 1.03-2.34; P = 0.038] compared with the G allele. Under a dominant model of inheritance, the carriage of at least one T allele was significantly more frequent in patients with achalasia (80.7%) than in controls (65.3%; OR: 2.21; 95% CI, 1.13-4.33; P = 0.022). No association of the c-kit rs2237025 polymorphism with achalasia was detected. Conclusions & Inferences Despite the small sample size and the possibility of a false positive finding, our preliminary data support the hypothesis that the T allele of the c-kit rs6554199 polymorphism may be associated with achalasia in the Turkish population. These findings need to be replicated in other racial-ethnically diverse populations.Publication Open Access Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease(ELSEVIER SCIENCE BV, 2011-02) EREN, FATİH; Akin, Hakan; Tahan, Gulgun; Ture, Filiz; Eren, Fatih; Atug, Ozlen; Tahan, Veysel; Hamzaoglu, Ismail; Imeryuz, Nese; Tozun, Nurdan; Hamzaoglu, Hulya OverBackground: Increasing Increasing evidence suggests that innate immune system may have a key role in the pathogenesis of the inflammatory bowel disease (IBD). Bactericidal/permeability increasing protein (BPI) has an important role in the recognition and neutralization of gram-negative bacteria by host innate immune system. The polymorphism on BPI gene called Lys216Glu is on the suspected list of IBD pathogenesis. Methods: We studied the Lys216Glu polymorphism on BPI gene, in a Turkish IBD patient population. A total of 238 IBD patients; 116 Crohn's disease (CD) and 122 ulcerative colitis (UC), besides 197 healthy controls were included in this study. Results: The Glu/Glu genotype and allele frequencies were found to be statistically higher compared to healthy control group not only in CD patients [P: 0.03, OR: 1.87 (CI 95% 1.02-3.42) and P: 0.00001 (OR: 2.07 CI 95% 1.47-2.91) respectively] but also in UC patients [P: 0.0002, OR: 2.71 (CI 95% 1.53-4.80) and P: 0.00002 (OR: 2.71 CI 95% 1.53-4.80) respectively]. Conclusions: BPI polymorphism (Lys216Glu) is associated both to CD and UC. Our findings differ from the two Western European studies; one without any association and the other indicating an association only with CD. Our study is the first one reporting a novel association between BPI gene mutation (Lys216Glu) and UC. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.Publication Metadata only Serum osteopontin levels as a predictor of portal inflammation in patients with nonalcoholic fatty liver disease(ELSEVIER SCIENCE INC, 2013) EREN, FATİH; Yilmaz, Yusuf; Ozturk, Oguzhan; Alandab, Yesim Ozen; Senates, Ebubekir; Colak, Yasar; Doganay, Hamdi Levent; Coskunpinar, Ender; Oltulu, Yasemin Musteri; Eren, Fatih; Atug, Ozlen; Tuncer, Ilyas; Imeryuz, NeseBackground: Osteopontin is a secreted phosphorylated glycoprotein that is expressed by a variety of cell types and that mediates numerous and diverse biological functions. Osteopontin knockout mice are protected from obesity-induced hepatic steatosis. In the present study, we sought to investigate whether serum osteopontin concentrations are associated with liver histology in patients with nonalcoholic fatty liver disease. Methods: Serum levels of osteopontin were measured by enzyme-linked immunosorbent assay in 179 Well-characterized patients with nonalcoholic fatty liver referred for liver histology and 123 control subjects. Results: Serum osteopontin levels were markedly higher in patients with nonalcoholic fatty liver disease than in controls (p < 0.001). Multivariable analysis showed that osteopontin levels were strongly and independently associated with both portal inflammation (beta = 0.294, p < 0.01) and serum aminotransferase levels (aspartate aminotransferase: beta = 0.295, p < 0.01; alanine aminotransferase; beta = 0.285, p < 0.01). Conclusion: In summary, these data demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty liver disease and are a significant independent predictor of portal inflammation in this clinical entity. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Publication Open Access Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity(ELSEVIER SCIENCE BV, 2011-10) EREN, FATİH; Yilmaz, Y.; Yonal, O.; Eren, F.; Atug, O.; Hamzaoglu, H. OverInteraction of the receptor for advanced glycation endproducts (RAGE) with its ligands results in expression of inflammatory mediators, activation of NF-kappa B, and induction of oxidative stress, all of which have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of inflammation in numerous RAGE-mediated disorders. Objective: To assess sRAGE levels in adult patients with IBD. Method: Serum was collected from adult patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60 patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were determined by enzyme-linked immunosorbent assay. Results: Serum sRAGE levels were elevated in IBD compared to HC and were higher in UC patients compared to CD and HC. Levels of sRAGE were significantly higher in the serum of UC patients with active disease compared to patients with inactive disease, but no association with the Montreal Classification was evident. Serum sRAGE was lower in CD patients with biological therapies. Conclusions: These findings suggest that serum levels of sRAGE are altered in patients with intestinal inflammation and may reflect distinct immunoinflammatory pathogenesis of UC and (C). 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.Publication Metadata only Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease(PERGAMON-ELSEVIER SCIENCE LTD, 2012) EREN, FATİH; Eren, Fatih; Kurt, Ramazan; Ermis, Fatih; Atug, Ozlen; Imeryuz, Nese; Yilmaz, YusufObjectives: We sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) - an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis - are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). Design and methods: Serum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls. Results: FGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130 pg/mL) than in controls (median: 210 pg/mL, P<0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r = -0.25. P<0.05) but not after adjustment for potential confounders (beta = -0.18; t = 1.78, P = 0.08). Conclusions: This pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.Publication Metadata only Serum Levels of Adipokines in Patients with Chronic HCV Infection: Relationship with Steatosis and Fibrosis(ELSEVIER SCIENCE INC, 2009) ÇELİKEL, ÇİĞDEM; Tiftikci, Arzu; Atug, Ozlen; Yilmaz, Yusuf; Eren, Fatih; Ozdemir, Filiz Ture; Yapali, Suna; Ozdogan, Osman; Celikel, Cigdem Ataizi; Imeryuz, Nese; Tozun, NurdanBackground and Aims. Hepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection. Methods. We examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4 +/- 5 kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2 +/- 3 kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA. Results. HCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1 a in two patients (3.9%), 1 c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders. Conclusions. Patients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group. (C) 2009 IMSS. Published by Elsevier Inc.Publication Metadata only No association between the functional cannabinoid receptor type 2 Q63R variants and inflammatory bowel disease in Turkish subjects(AVES, 2014) EREN, FATİH; Yonal, Oya; Eren, Fatih; Yilmaz, Yusuf; Atug, Ozlen; Over, Hulya HamzaogluBackground/Aims: The endocannabinoid system can exert beneficial effects on gastrointestinal inflammation, and cannabinoid receptor-2 (CB2) agonists may represent a new therapeutic approach in inflammatory bowel disease (IBD). A functional CB2 Q63R polymorphism (rs35761398) in the CNR2 gene has been shown to affect the immunomodulating properties of the CB2 receptor. We sought to investigate whether the functional CB2 Q63R polymorphism (rs35761398) is associated with IBD susceptibility in a Turkish clinical sample. Materials and Methods: A total of 202 IBD patients, comprising 101 Crohn's disease (CD) patients and 101 ulcerative colitis (UC) patients, and 101 healthy controls were included in the study. The CB2 Q63R polymorphism was genotyped using real-time PCR. Results: There were no significant differences in the genotype frequencies of the three study groups. The odds ratio of the minor Q allele for CD relative to the common R allele was not significant (OR = 1.02, 95% CI = 0.67-1.56, p=0.99). Similarly, the odds ratio of the minor Q allele for UC relative to the common R allele did not reach statistical significance (OR = 1.10, 95% CI = 0.72-1.68, p=0.75). Moreover, the genotype frequencies did not show any significant association with the disease extent in either CD (p=0.71) or UC patients (p=0.59). Conclusion: These pilot findings suggest that CB2 Q63R polymorphism does not play a major role in genetic susceptibility to IBD or in its disease phenotypes among Turkish subjects.Publication Open Access Bactericidal Permeability Increasing Protein Gene Polymorphism is Associated with Inflammatory Bowel Diseases in the Turkish Population(MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2015) EREN, FATİH; Can, Guray; Akin, Hakan; Ozdemir, Filiz T.; Can, Hatice; Yilmaz, Bulent; Eren, Fatih; Atug, Ozlen; Unsal, Belkis; Hamzaoglu, Hulya O.Background/Aims: Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients. Patients and Methods: The present study included 528 inflammatory bowel disease patients, 224 with Crohn's disease and 304 with ulcerative colitis, and 339 healthy controls. Results: Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn's disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease. Conclusions: Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn's disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn's disease.Publication Metadata only R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History(SPRINGER, 2010) ÇELİKEL, ÇİĞDEM; Eren, Fatih; Akkiprik, Mustafa; Atug, Ozlen; Sonmez, Ozgur; Tahan, Gulgun; Ozdemir, Filiz; Hamzaoglu, Hulya Over; Celikel, Cigdem Ataizi; Imeryuz, Nese; Avsar, Erol; Ozer, AyseP53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR=3.03; 95%CI=1.91-2.40; p=0.003), but only modest association with UC (OR=1.61; 95%CI=0.98-2.65; p =0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR=8.0; 95%CI=1.68-38.08, p=0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR=17.77; 95%CI=0.98-323.34, p=0.012) and steroid use (OR=10.14; 95%CI=2.63-39.12, p=0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.