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Öğe Association with Leptin Gene c.-2548 G>A Polymorphism, Serum Leptin Levels, and Body Mass Index in Turkish Obese Patients(Humana Press Inc, 2013) Sahin, Deniz Say; Tumer, Cemil; Demir, Cemil; Celik, M. Murat; Celik, Mustafa; Ucar, Edip; Gunesacar, RamazanLeptin is a protein hormone which plays a critical role in the regulation of both body-weight through reducing food intake and stimulating energy expenditure. Several polymorphisms in leptin gene (LEP), which encodes for leptin, have been described. However, its association with obesity is still controversial. Therefore, in the present study, we aimed to investigate whether LEP c.-2548 G > A polymorphism was associated with serum leptin levels, lipid parameters, and body mass index in Turkish obese patients. Forty-seven obese patients and 48 healthy individuals were included in the study. Blood samples were collected for DNA extraction. LEP c.-2548 G > A polymorphism were detected using polymerase chain reaction-restriction fragment length polymorphism technique. Serum leptin levels and lipid parameters were measured by ELISA and enzyme colorimetric assay techniques, respectively. GA or AA genotypes and A allele carrier frequencies of the c.-2548 G > A polymorphism in the LEP were higher in obese (38.3, 34.0 and 72.3 %) when compared with controls (14.6, 12.5, and 27.1 %; p = 0.011, 0.016, and 0.002, respectively). On the other hand, AA or AG genotypes were also related to increased serum leptin levels (p < 0.001) and body mass index (p < 0.0001). All these consequences showed that LEP -2548 AA or AG genotypes are important predictors for increased levels of leptin and BMI in Turkish obese patients and it may be a useful marker for obesity risk in our population.Öğe Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients(Cukurova Univ, Fac Medicine, 2023) Gunesacar, Ramazan; Eksi, Durkadin Demir; Alpay, Ali Seydi; Hanikoglu, Ferhat; Erdogan, HalukPurpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA. Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2 & PLUSMN;11.49 pg/ml) than in controls (85.46 & PLUSMN;12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194 & PLUSMN;16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 & PLUSMN;14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5 & PLUSMN;8.67 ng/ml, 172.4 & PLUSMN;14.01 pg/ml, 159.3 & PLUSMN;10.19 pg/ml, respectively) than that those in the controls (104.5 & PLUSMN;9.182 ng/ml, 141.4 & PLUSMN;17.74 pg/ml, 100.1 & PLUSMN;11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients. Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.Öğe Evaluation of the mean platelet volume in children with familial Mediterranean fever(Springer Heidelberg, 2012) Arica, Secil; Ozer, Cahit; Arica, Vefik; Karakus, Ali; Celik, Tanju; Gunesacar, RamazanTo evaluate the Mean Platelet Volume (MPV) levels in children diagnosed with familial Mediterranean fever (FMF), during attack and attack-free periods. The records of a total of 117 children with FMF, diagnosed using the Tel-Hashomer criteria, have been scanned. The study consisted of 53 patients during an attack (group 1), 64 patients in attack-free period (group 2), and 57 healthy controls (group 3). Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded. The MPV and platelet values in FMF patients during attack (group 1) and FMF patients during attack-free periods (group 2) have been found to be significantly higher than those of the health control group (group 3). Positive correlation has been found between the MPV and platelet values in Group 1 and the disease's severity score (r = 0.224, and r = 0.268, respectively). Positive correlation (r = 0.528, and r = 0.485, respectively) has been also identified between MPV and blood platelet count in patients in Group 1 and 2. No correlation was found between the Colchicine treatment period and MPV (r = -0.005). The MPV values in the complete group of FMF diagnosed children have been found to be much higher compared to those in healthy children. As a consequence, we consider the MPV value as a useful marker that demonstrates the risk of early stage atherosclerosis in children with FMF.Öğe Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever(Elsevier Science Bv, 2017) Ozel, Emine Gulce; Duran, Gulay Gulbol; Celik, Muhammet Murat; Duran, Nizami; Gunesacar, RamazanFamilial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A > G (rs1800682, Mval) and Fas ligand gene (FASLG), NM_000639.2: c.-844C > T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A > G and FASLG c.-844C > T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A > G and FASLG c.-844C > T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS c.-671AG genotype or G allele and FASLG c.-844 allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant, higher frequencies of FASLG c.-844CC genotype in FMF patients may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression.Öğe Frequency of MEFV gene mutations in Hatay province, Mediterranean region of Turkey and report of a novel missense mutation (I247V)(Elsevier, 2014) Gunesacar, Ramazan; Celik, Muhammet Murat; Arica, Vefik; Elmacioglu, Sibel; Ozturk, Oktay HasanIn the present study, 1000 patients with clinical suspicion of FMF were retrospectively reviewed to determine the spectrum of MEFV gene mutations by using DNA sequence analysis between September, 2008 and April, 2012. Sixteen different mutations and 55 different genotypes were detected in 618 of 1000 patients. Among 16 different mutations, R202Q (21.35%) was the most frequently observed mutation; followed by E148Q (8.85%), M694V (7.95%), M680I (2.40%), V726A (1.85%), M694I (0.95%), A744S (0.80%), R761H (0.55%), P283L (0.35%), K695R (0.20%), E230K (0.15%), L110P (0.10%), I247V (0.05%), G196W (0.05%) and G304R (0.05%). In the present study, a novel missense mutation (I247V) and a silent variant (G150G) were identified in the MEW gene. On the other hand, P238L, G632A and G304R mutations are the first cases reported from Turkey. Our results indicated that MEW mutations are highly heterogeneous in our study population as in other regions of Turkey and mutation screening techniques such as PCR-RFLP, amplification refractory mutation system or reverse hybridization do not adequately detect uncommon or novel mutations. Therefore, it was proven that sequence analysis of the MEW gene could be useful for detection of rare or unknown mutations. (C) 2014 Elsevier B.V. All rights reserved.Öğe High prevalence of Staphylococcus aureus cultivation and superantigen production in patients with psoriasis(John Libbey Eurotext Ltd, 2009) Balci, Didem Didar; Duran, Nizami; Ozer, Burcin; Gunesacar, Ramazan; Onlen, Yusuf; Yenin, Julide ZehraThe aim of this study was to evaluate the association of Staphylococcal enterotoxins (se) a through e, exfoliative toxin (et) a and b, toxin and toxic shock syndrome toxin (tst) and mecA with psoriasis. We also investigated the distribution of Staphylococcus aureus (S. aureus) in the skin and nares. Fifty consecutive patients with chronic plaque-type psoriasis and 50 sex- and age-matched healthy controls were included in this study. There was a statistical difference in cultivation of S. aureus between lesional (64%) and non-lesional skin (14%) in patients with psoriasis (p = 0.037). S. aureus was cultivated from the nares in 25 (50%) of 50 patients with psoriasis and in 17 (34%) of 50 healthy controls (p > 0.05). In psoriasis patients, 31 (96.8%) out of the 32 strains isolated from the lesional skin and 3 (42.3%) out of the 7 strains isolated from the non-lesional skin were toxigenic (p = 0.01). Isolated strains from the nares were toxigenic in 96% (24/25) for patients with psoriasis and in 41.2% (7/17) for healthy controls, respectively (p = 0.006). Patients with cultivation-positive in lesional skin had a significantly higher PASI score than patients who were cultivation-negative in lesional skin (8.28 +/- 3.97 vs. 5.89 +/- 2.98, p = 0.031). Our results confirm that S. aureus colonization and its toxigenic-strains are associated with psoriasis. According to our findings, non-classical superantigens such as methicillin resistance gene (mecA), see and etb may also be associated with psoriasis.Öğe The importance of the M470V polymorphism(Dr Behcet Uz Cocuk Hastaliklari Ve Cerrahisi, 2017) Celik, Tanju; Gunesacar, Ramazan; Balci, Ali; Unal, Sule; Aldic, Guliz; Eskici, Harika; Atilgan, NigarObjective: Several hundreds of cystic fibrosis transmembrane conductance regulator (CFTR) variants have been reported, however it is not known whether which one of them was causing the disease of cystic fibrosis (CF) or not. Information about CFTR genes carrying the M470 or the V470 allele are interesting. In this study, we aimed to investigate the clinical importance of M470V mutation in Antiochia region. Methods: A case-control study consisted of 145 children from whom CF gene study was requested because of recurrent respiratory tract infections, growth failure, chronic diarrhea and constipation. The parameters of patients with positive mutation were compared with negative ones as for gender, age, height, weight, annual number of upper and lower respiratory tract infections, parental consanguinity, sibling death, clinical and laboratory parametres. Results: In 63 of 145 patients (43.4%), heterozygous mutation, in 16 (11%) of them homozygous mutation was detected. All of the patients with mutation group had M470V mutation. The sweat test results of all patients were within normal limits. Mean age of those patients were 41.21 +/- 39.8 (min: 6 max: 192) months and 30 (38%) of them were girls. Thirty percent of the patients with mutation (n=17.7) had a familial history of cystic fibrosis, 2 a history of sibling death. In the mutation group, only annual number of infections, skin dryness, loss of weight, level of IgG and IgM were significantly higher (p<0.05). Conclusion: It was concluded that in M470V positive cases, the disease may cause clinical symptoms without affecting sweat test results, with less gastrointestinal but more respiratory symptoms, causing a more prominent loss of weight.Öğe Investigation of C5a receptor gene 450 C/T polymorphism in Turkish patients with familial Mediterranean fever(Springer, 2010) Erken, Eren; Gunesacar, Ramazan; Ozer, Huseyin T. E.Familial Mediterranean fever (FMF) is a genetic disorder with acute inflammatory serosal attacks due to MEFV gene mutations which resides in chromosome 16. Lack of a C5a inhibitor activity in the peritoneum has previously been proposed in part to contribute in propagation of the serosal inflammation in FMF attacks. The aim of this study is to investigate C5a receptor (C5aR) gene polymorphism in patients with FMF and its relation to the main features of the disease. A polymorphism in the coding region of C5aR gene leading to C to T transition at nucleotide position 450 has been investigated in 85 non-related Turkish FMF patients and 160 non-related healthy controls by using PCR-RFLP. The frequencies of C5aR gene 450 CT genotype and T allele were not significantly different between Turkish FMF patients and healthy subjects (14.12 and 8.24% for FMF vs. 10 and 5% for controls, respectively). C5aR gene 450 CT genotype tended to associate with the presence Henoch-Schonlein purpura (OR: 1.25, 95% CI: 0.917-1.704, P = 0.017) but with no other clinical findings of the disease. C5aR polymorphism might be searched in populations having high prevalence of FMF.Öğe Investigation of the clinical and hematological significance of the first observed hemoglobin Ernz variant [?123(H1) Thr>Asn] in the Turkish population(Tubitak Scientific & Technological Research Council Turkey, 2012) Gunesacar, Ramazan; Celik, Muhammet Murat; Ozturk, Oktay Hasan; Celik, Mustafa; Tumer, Cemil; Celik, TanjuAim: In this report, we aimed to investigate the clinical and hematological significance of the first observed hemoglobin Ernz variant in the Turkish population. Materials and methods: We identified the Hb Ernz variant in 3 nonrelated females (Probands 1, 2, and 3). Proband l's family was also included the study. Hematological data were obtained with an automated cell counter and routine methodology. The beta-globin gene was sequenced by automatic sequencing. Results: Proband 1 was detected as a combination of Hb Ernz/Hb S without any clinical symptoms. Her sister and brother had to be an Hb Ernz/Hb S combination. Her mother and father only showed Hb Ernz and Hb S, respectively. Proband 2 had the Hb Ernz variant with IVS-I 5nt homozygous alpha 2 gene mutation. Proband 3 had a heterozygous Hb Ernz variant. All subjects were clinically and hematologically normal but Proband 2 had low hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and high red blood cell distribution width levels. Conclusion: In the present study, the Hb Ernz variant is demonstrated for the first time in the Turkish population. Additionally, there is no published report in the world literature of Hb Ernz in combination with IVS-I 5nt homozygote mutation in the alpha-globin gene or Hb S variant. The present report shows that the Hb Ernz variant is not clinically or hematologically significant.Öğe Investigation of the Relation Between FAS, FASLG Polymorphisms and Serum Fas, FasL Levels in Patients with Psoriasis(Univ Press, 2018) Duran, Gulay Gulbol; Kasap, Mulkiye; Gunesacar, Ramazan; Dogramaci, Asena Cigdem; Denli, Yasar GulBackground: Psoriasis is a multifactorial and inflammatory chronic skin disease indicated with T-cell-mediated keratinocyte hyper-proliferation. Demographic, epidemiological (family, twin), serological, and genetic studies have clearly demonstrated that psoriasis is a polygenic and multifactorial disease. Aim: The objectives of the study are; to determine the prevalence of the polymorphisms of FAS (Fas cell surface receptor gene) -671 A>G (rs: 1800682) and FASLG (Fas ligand gene) -844 T>C (rs: 763110), to investigate the serum levels of sFas and sFasL, and also to discover any relationship between gene polymorphisms and serum levels in psoriatic patients. Material and Methods: 50 treated and 69 untreated patients, and 140 healthy controls were included in the study. Polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The serum levels were measured in randomly selected treated (39) and untreated (40) patients, also in 84 healthy controls using micro-ELISA technique. Results: There was no statistical difference between polymorphisms in the patient and control groups. However, sFas and sFasL levels in both treated and untreated patients were higher than that of the controls. Conclusion: The investigated FAS and FASLG polymorphisms were not found to be directly associated with the psoriasis. Elevated sFas and sFasL levels in psoriatic patients showed that these factors may possess a significant role in the pathogenesis of psoriasis.Öğe Spectrum of a-thalassemia mutations including first observation of - -FIL deletion in Hatay Province, Turkey(Academic Press Inc Elsevier Science, 2013) Celik, Muhammet Murat; Gunesacar, Ramazan; Oktay, Gonul; Duran, Gulay Gulbol; Kaya, HasanAlpha thalassemia (alpha-thal) is one of the most common genetic disorders in the world. It is characterized by the absence or reduced expression of alpha-globin genes. The frequency of alpha-thal mutations in the province of Hatay in South Turkey is unknown. Therefore, in the present study, we aimed to investigate the spectrum of alpha-thal mutations in this province. Three hundred and nine patients were tested for alpha-thal mutations by using reverse dot blot hybridization technique and nine different mutations were detected in 97 of them. Among the 9 different mutations found, the most frequent mutations were the -alpha(3.7) (43.81%), -alpha 2(-5nt) (6.70%), - -(MED) (5.67%) and alpha 2(Poly) (A2) (2.57%). In the present study, - -(FIL) mutation was detected in a patient for the first time in Turkey. Our results indicated that alpha-thal mutations are highly heterogeneous and -alpha(3.7) is the most prevalent mutation in Hatay province of South Turkey. In addition, - -(FIL) mutation was detected in a patient for the first time in Turkey. This new finding may contribute to the establishment of a national mutation database and genetic counseling. (C) 2013 Elsevier Inc. All rights reserved.Öğe Structure, Function, Molecular Genetics, Disease Associations and Therapeutic Potential of Mannose Binding Lectin: Review(Ortadogu Ad Pres & Publ Co, 2011) Gunesacar, Ramazan; Tastemir, Deniz; Yildirim, Ayse; Eryilmaz, NaciyeMannose binding lectin (MBL) which is a collagen like serum protein and primarily synthesized by the liver is a significant component of natural immune response. MBL molecule provides phagocytosis of those microorganisms by macrophages or activates the lectin pathway of complement system via C3 convertase by binding on sugar groups on the surfaces of multifarious microorganisms. The MBL2 gene is located on chromosome 10 at position 10q11.2-q21 and consists of four exons and three introns. Three genetic variations named as allel B (codon 54, GGC > GAC, Gly > Asp), allel C (codon 57, GGA > GAA, Gly > Glu) and allel D (codon 52, GCT > TGT, Arg > Cys) and affecting the serum levels and trimerization of MBL protein were detected on the first exon of MBL2 gene. An association was shown between MBL2 gene codon variants or low MBL serum levels and bacterial, viral and fungal infections or autoimmunity development. An association was also detected between high MBL serum levels and renal graft rejection, diabetic nephropathy and inflammatory diseases. In this review, relationships between MBL and diseases and therapeutic potential of the molecule were summarized along with the molecular structure, function and genetics of MBL.
