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Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent short episodes (1–3 days) of inflammation and fever. FMF is associated with MEFV gene mut...

Lung cancer is one of the deadliest types of cancers and genetic and epigenetic alterations play major roles in its development. Chromodomain (CHD) protein family acts in chromatin organization, regulation of transcription and also genomic stability and cancer prevention. Although CHD5, a member of this family was shown to contribute to major cellular events and functions as a tumor suppressor gene in various types of cancer, it is not clear whether CHD5 plays a role in lung carcinogenesis. The aim of this study was to investigate the possible role of CHD5 in progression of non-small cell lung cancer (NSCLC). Expression levels of CHD5 gene in 59 tumor and corresponding non-cancerous lung tissue samples were analyzed by qRT-PCR and the methylation status of the promoter region was investigated by methylation specific PCR (MS-PCR). The Akt phosphorylation levels were investigated by Western Blot (WB). CHD5 was down-regulated in 17 (39.5%) and up-regulated in 24 (55.8%) of tumor specimens. Even though the promoter of CHD5 was hypermethylated in 8 patients, it was not found associated with CHD5 gene expression (p=0.08). Akt phosphorylation was increased in 14 (53.8%) and decreased in 12 (46.2%) of the samples but no significant association was found between p-Akt phosphorylation and CHD5 expression (p=0.67). We suggest that CHD5 may act as a tumor suppressor gene in NSCLC.

Background: Lung cancer is the leading cause of cancer deaths. The main risk factor is smoking but the risk is also associated with various genetic and epigenetic components in addition to environmental factors. Increases in the gene copy numbers due to chromosomal amplifications constitute a common mechanism for oncogene activation. A gene-dense region on chromosome 11q13 which harbors four core regions that are frequently amplified, has been associated with various types of cancer. The important cell cycle regulatory protein cyclin D1 (CCND1) is an essential driver of the first core region of the Chr11q13 amplicon. Deregulation of CCND1 has been associated with different kinds of human malignancies including lung cancer. The EMSY (c11orf30) gene has been proposed as the possible driver of the fourth core of the 11q13 amplicon and its amplification has been associated with breast and ovarian cancers. There is no report in the literature investigating the EMSY gene in lung cancer. Methods: In this study, expression levels of the EMSY and CCND1 genes were investigated in 85 patients with non small cell lung cancer by Real Time PCR. Results: Expression of the EMSY and CCND1 genes were increased in 56 (65.8%) and 50 (58.8%) of the patients, respectively. Both genes showed a higher expression in the tumors when compared to normal tissues. A strong correlation was present between the expression rates of both genes (p

Despite therapeutic advances, lung cancer remains one of the most common causes of cancer‐related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11‐12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non‐small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT‐PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up‐regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.

The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM).116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively.Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p0.001).According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

Introduction Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by persistent airflow limitation and is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Interleukin-1 beta (IL-1β) is a major pro-inflammatory cytokine expressed by many cells such as macrophages, neutrophils and monocytes and functions in cellular activities such as proliferation, differentiation and apoptosis. Recent studies demonstrate controversial results about the relationship between IL-1β and COPD. The aim of this study is to investigate the association between IL-1β -511 (rs 16944) and +3954 (rs 1143634) gene polymorphisms and COPD in Turkish population. Materials and Methods A total of 152 subjects were recruited in the study and divided into three groups: 72 COPD patients, 41 healthy smokers and 39 never-smokers. PCR-RFLP method was used to determine the allele frequencies, genotype and haplotype distributions. Result We did not find any significant difference between the gene polymorphisms and COPD by means of genotype frequencies, haplotype association, stage, gender or smoking status (p< 0.05). Conclusions Our results do not show any evidence of association between COPD and IL-1β -511 and +3954 gene polymorphisms in Turkish population.

Background Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes. Subjects and methods To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively. Results We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p = 0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p = 0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p = 0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines. Conclusions We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.

Lung cancer is the most common cause of cancer-related death worldwide and, like many other cancers, is affected by different genetic, epigenetic, and environmental factors. The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3-24.1, and it has been shown that it loses its function due to alterations in genetic and epigenetic mechanisms. The aim of this study is to investigate the relationship between lung cancer and WWOX gene. Tumor tissue samples, corresponding normal tissues, and blood samples obtained from 50 lung cancer patients were involved in the study. We analyzed methylation profile by methylation-specific PCR and mutations and polymorphisms by DNA sequencing. Methylation analysis showed that promoter hypermethylation was present in 38 of 50 (76%) patients. In addition, promoter region of WWOX gene of younger patients was more frequently methylated than older patients. Using DNA sequencing, we found four genetic alterations in WWOX gene. Two of them were germline mutations (Exon 4 and 7), and two of them were polymorphic (Exon 6 and 8). We found a new mutation in exon 7 (Arg-254--Cys) which has not been described previously. The changes in the short-chain dehydrogenase domain of the protein caused by the genetic alterations may affect the function of the gene. We conclude that hypermethylation of WWOX gene promoter region and mutations in the gene might be related to lung carcinogenesis.

About 10% of patients with severe hemophilia exhibit a milder clinical phenotype with less frequent bleeds. Among many other factors, coinheritance of prothrombotic mutations have been proposed to act as modulators of clinical severity in severe hemophilia. We conducted a study to evaluate the impact of 3 prothrombotic mutations (factor V Leiden, factor II, and methylenetetrahydrofolate reductase mutations) on clinical phenotype of patients with severe hemophilia in our institution. For this purpose we compared the average annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. A total of 38 hemophilia A and B patients with factor levels less than 1 were recruited between October 2006 and October 2007. Prothrombotic mutations were detected in venous blood using polymerase chain reaction amplification technique. Eighteen patients (47%) carried no prothrombotic mutations. The remaining 20 patients (53%) were found to be carriers of either 1 or 2 mutations. Median age in both carrier and the non-carrier groups was 27 years. None of the patients in either group gave a history of thromboembolic event. Median annual factor concentrate consumptions in carriers and noncarriers were 610 ± 530 units/kg and 770 ± 670 units/kg, respectively ( P = .203). Our results demonstrated no significant difference in annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. Considering that average annual factor consumption is a surrogate indicator of clinical phenotype, we concluded that coinheritance of prothrombotic mutations was not associated with occurrence of different clinical phenotypes in severe hemophilia.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the most common medically intractable epilepsy syndromes and the pathogenesis of HS remains highly obscure. Recent studies demonstrated controversial results about the relationship between interleukin (IL) gene polymorphism and epilepsy in different ethnic groups. This correlation was investigated in Turkish patients with MTLE-HS. The allele distribution of IL-1alpha and IL-1beta in 47 patients of Turkish ancestry was determined and compared with 99 ethnically matched control subjects. Analysis of genotype frequencies between patients and controls showed no statistically significant difference (p0.05). Our data suggest that IL-1alpha and IL-1beta gene polymorphisms do not act as a strong susceptibility factor for MTLE-HS in individuals of Turkish ancestry.

Recent studies focusing on the genetic influences on outcome after head injury (HI) have suggested that different alleles of certain genes are associated with different outcomes. Interleukin-1 beta (IL-1beta) gene, especially beta2 polymorphism, is frequently observed in Alzheimer's disease, a remarkable degenerative state in which HI is among the known risk factors. Therefore, the aim of this paper was to search for the possible association between the outcome and IL-1beta gene polymorphism in human HI.The study group was composed of the 69 patients admitted to the neurosurgery department after HI. The severity of the initial injury was evaluated by means of the Glasgow Coma Scale and outcome six months later was assessed by means of the Glasgow Outcome Scale. IL-1beta genotypes were determined from blood samples by standard methods.Fourteen of 25 (56%) patients with IL-1beta +3953 allele 2 had an unfavourable outcome (dead, vegetative state or severe disability) compared with eight of 44 (18.1%) patients without IL-1beta +3953 (p = 0.0004). Similarly, 20 of 28 (71.4%) patients with IL-1beta -511 allele 2 had an unfavourable outcome compared with two of 41 (4.8%) patients without IL-1beta -511 (p = 0.005). Patients who had a composite of IL-1beta 2/2 or 1/2 genotype from both -511 and +3953 region of the chromosome 2 were more prone to have bad prognosis.Results of our study demonstrated that there might be a significant association between IL-1beta gene polymorphism and outcome after HI, supporting the hypothesis of a genetically determined influence.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.

Buyru, Nur/0000-0002-6920-1455; Baykara, Onur/0000-0002-9754-8456; Uzan, Mustafa/0000-0001-7214-380X; Sanus, Galip Zihni/0000-0001-6539-7254 WOS: 000234773600003 PubMed: 16378839 Background: Interleukin (IL) I is a proinflammatory cytokine that has been identified as an important mediator of neurodegeneration induced by ischemia or traumatic brain injury. Accumulating evidence to date has suggested that the major cytokine contributing to neurodegeneration after head injury is IL-1 beta rather than IL-1 alpha; however, there is no sufficient data regarding IL-1 alpha in literature, and there may be an association between IL1A gene polymorphism and outcome after head injury. Methods: We performed a prospective clinical study and included a recruited series of 71 patients who had head injury and were admitted to our neurosurgical unit. Severity of initial injury was assessed by the Glasgow Coma Scale. Outcome at 6 months after injury was assessed by means of the Glasgow Outcome Score. Interleukin la genotypes were determined from blood samples by standard methods. Results: Of 40 patients with ILIA*2, 18 (45%) had an unfavorable outcome (dead, vegetative state, or severe disability) compared with 7 (22.5%) of 31 without ILIA*2 (P =.08). Conclusion: Our findings show that there is no genetic association between ILIA gene polymorphism and outcome after head injury. Further clinical studies should be designed to confirm and further evaluate these findings. (c) 2006 Elsevier Inc. All rights reserved.