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    Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case-control study
    (Dove Medical Press Ltd, 2016) Coskun, Salih; Varol, Sefer; Ozdemir, Hasan H.; Celik, Sercan Bulut; Balduz, Metin; Camkurt, Mehmet Akif; Cim, Abdullah
    Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine prointerleukin-1 beta, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5' nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21-0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06-69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility.
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    Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine
    (Dove Medical Press Ltd, 2016) Coskun, Salih; Varol, Sefer; Ozdemir, Hasan H.; Agacayak, Elif; Aydin, Birsen; Kapan, Oktay; Camkurt, Mehmet Akif
    Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case-control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5'-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] = 0.723 [0.523-0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] = 1.626 [1.117-2.365] or P=0.007, ORs [95% CIs] = 1.610 [1.140-2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.
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    Association of Polymorphisms within the Serotonin Receptor Genes 5-HTR1A, 5-HTR1B, 5-HTR2A and 5-HTR2C and Migraine Susceptibility in a Turkish Population
    (Korean Coll Neuropsychopharmacology, 2016) Yucel, Yavuz; Coskun, Salih; Cengiz, Beyhan; Ozdemir, Hasan H.; Uzar, Ertugrul; Cim, Abdullah; Camkurt, M. Akif
    Objective: Migraine, a highly prevelant headache disorder, is regarded as a polygenic multifactorial disease. Serotonin (5 HT) and their respective receptors have been implicated in the patogenesis. Methods: We investigated the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor gene polymorphisms and their association with migraine in Turkish patients. The rs6295, rs1300060, rs1228814, rs6311, rs6313, rs6314, rs6318, rs3813929 (-759C/T) and rs518147 polymorphisms were analyzed in 135 patients with migraine and 139 healthy subjects, using a BioMark 96.96 dynamic array system. Results: We found no difference in the frequency of the analyzed eight out of nine polymorpisms between migraine and control groups. However, a significant association was found between the rs3813929 polymorphism in the promoter region of 5-HTR2C gene and migraine. Also, the allele of rs3813929 was more common in the migraine group. Conclusion: This result suggests that the 5-HTR2C rs3813929 polymorphism can be a genetic risk factor for migraine in a Turkish population.
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    Changes in serum albumin levels and neutrophil-lymphocyte ratio in patients with convulsive status epilepticus
    (Taylor & Francis Ltd, 2017) Ozdemir, Hasan H.; Akil, Esref; Acar, Abdullah; Tamam, Yusuf; Varol, Sefer; Cevik, Mehmet Ugur; Arikanoglu, Adalet
    Aim: Inflammation may be involved in the ictogenesis and development of some partial epilepsies. Serum albumin levels and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation. The aim of this study was to investigate the ability of serum albumin levels and NLR to predict inflammation in patients with convulsive status epilepticus (CSE). Methods: This retrospective study was conducted on 58 patients who were diagnosed with CSE and control group comprised of 58 healthy individuals. Albumin levels and NLR were evaluated during both the acute and subacute periods of CSE. Results: The average serum albumin levels were 3.27 +/- 0.62 g/dL during the acute period and 3.4 +/- 0.67 g/dL in the subacute period in the patient group and 3.92 +/- 0.52 g/dL in the control group. Neutrophil counts were higher in patients in the acute phase of CSE, but lymphocyte counts were lower compared to the control group and the subacute phase. The average NLR values were 4.83 +/- 5.1 in the acute period, 3.07 +/- 3.02 during the subacute period and 1.98 +/- 0.42 in the control group. Serum albumin and NLR levels were significantly different between the patients in the subacute and acute periods of CSE and the control group (p < 0.05). There were significant negative correlational relationships between serum albumin and NLR levels (p < 0.05). Conclusion: We found serum albumin levels were significantly lower and the NLR was significantly higher in the acute period of CSE. Neutrophil-mediated inflammation may be important in the aetiopathogenesis of CSE.
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    Contribution of polymorphisms in ESR1, ESR2, FSHR, CYP19A1, SHBG and NRIP1 genes to migraine susceptibility in Turkish population
    (Indian Acad Sciences, 2016) Coskun, Salih; Yucel, Yavuz; Cim, Abdullah; Cengiz, Beyhan; Oztuzcu, Serdar; Varol, Sefer; Ozdemir, Hasan H.
    Migraine, a highly prevalent headache disorder, is regarded as a polygenic multifactorial disease, Single-nucleotide polymorphisms (SNPs) in the genes that involved in sex hormone metabolism may comprise risk for migraine, but the results of previous genetic association studies are conflicting. The aim of this study was to evaluate genetic variants in genes involved in oestrogen receptor and oestrogen hormone metabolism in a Turkish population. A total of 12 SNPs in the ESR1, ESR2. FSHR, CYP19A1 SHBG and NRIP1 genes were genotyped in 142 migraine cases and 141 nonmigraine controls, using a 13iolVtark 96,96 dynamic array system. In addition, gene gene interactions were analysed using generalized multifactor dimensionality reduction (GMDR) methods. According to GI\ADR analysis, our results indicated that there was a significant association between migraine and gene gene interaction a.mong the CYP19A1 FSHR, ESR1 and NRIP1, Single-gene variant analysis showed that a significant association was observed between the TT genotype of rs10046 and migraine susceptibility. When the analysis was performed only in women, the GG genotype of rs222974I was different between migaineurs and controls. When the female migraine patients were divided into two groups, migraine related to menstruation ilVIRM) or migraine not related to menstruation (MN RN), OG genotype of rs726281 was significantly associated with M FM. These results suggested that rs10046 could play a potential role in migyaine susceptibility in Turkish population, Also, the rare GG genotype of rs726281 appears to influence migraine susceptibility in a recessive manner in MRM subgroup of female patients. In addition, variant GG genotype of rs2229741 may reduce the risk of migraine in Turkish women.
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    Evaluation of cerebral venous thrombosis secondary to oral contraceptive use in adolescents
    (Springer-Verlag Italia Srl, 2015) Ozdemir, Hasan H.; Varol, Sefer; Akil, Esref; Acar, Abdullah; Demir, Caner F.
    Our goal was to evaluate the clinical patterns, additional risk factors, treatment and outcome of cerebral venous thrombosis (CVT) related to adolescent oral contraceptive pill (OCP) usage. We evaluated 22 patients with CVT related to OCPs admitted to Firat and Dicle University Hospitals from January 2008 to January 2013. We assessed the clinical features, risk factors, imaging results and prognosis. Magnetic resonance imaging (MRI) and magnetic resonance were the preferred procedures for the diagnosis of CVT. MRI revealed parenchymal lesions in 11 (50 %) patients, and the remaining patients had normal MRIs. The sinuses most frequently affected by thrombosis were the superior sagittal sinus and the transverse sinus. The additional risk factors identified for CVT were antiphospholipid syndrome, protein C deficiency, protein C and S deficiency, factor V Leiden associated with heterozygous antithrombin III deficiency, methylenetetrahydrofolate reductase and prothrombin gene mutations. CVT may be overlooked in adolescents because it is more common among middle-aged and elderly adults. CVT should be suspected in the presence of neurological symptoms in adolescents, especially in those using OCPs.