Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

Proteomic analysis of the anticancer effect of various extracts of endemicThermopsisturcica in human cervical cancer cells

Background/aim: Thermopsisturcica is a perennial species endemic to Turkey and different extracts of T. turcica have an antiproliferative effect on cancer cells, but there has not been any report on HeLa (human cervical cancer) cells. Materials and methods: To get a better understanding of the molecular mechanism of anticancer activity of methanolic extracts of leaves (LE) and flowers (FE) of T. turcica, we employed 2-DE-based proteomics to explore the proteins involved in anticancer activity in HeLa cells. Results: T. turcica extracts showed a potent cytotoxic effect on HeLa cells with the IC50 values of 1.75 mg/mL for LE and 3.25 mg/mL for FE. The induction of apoptosis by LE and FE was also consistent with increased expression of caspase mRNAs and DNA fragmentation. In terms of the proteomic approach, 27 differentially expressed proteins were detected and identified through MALDI-TOF/TOF mass spectrometry. These altered proteins were involved in cytoskeleton organization and movement, protein folding, proteolysis and translation, cell cycle and proliferation, signal transduction, cell redox homeostasis, and metabolism. Conclusion: Up-regulation of protein disulfide isomerases and down-regulation of Rho GDP-dissociation inhibitor, heterogeneous nuclear ribonucleoproteins, and heat shock proteins may contribute to the induction of apoptosis and arresting of the cell cycle in HeLa cells.

Relationship between SIRT1 gene expression level and disease in age-related cataract cases

Background/aim: Age-related cataract is the most important visual impairment all over the world. Epigenetic modifications, especially overexpression of histone deacetylases, have become the focus of interest for cataract development in recent years. Sirtuin 1 (SIRT1), a class II histone deacetylase and a member of the sirtuin family, is one of the best-characterized histone deacetylases and has a pivotal role in age-related diseases. However, the association of SIRT1 with age-related cataracts has not yet been fully elucidated. Therefore, we aimed to determine the expression of SIRT1 in age-related cataract patients. Materials and methods: Expressions of SIRT1 were evaluated by quantitative polymerase chain reaction (qPCR) in patients and healthy controls. RNA samples were collected from the anterior capsule and peripheral blood samples of age-related cataract patients. Human lens epithelial cell line B3 and peripheral blood samples of healthy subjects were used as controls. Results: We determined that the expression of SIRT1 in blood and anterior capsule samples increased significantly compared to the control group (P < 0.05). Conclusion: The expression level of SIRT1 plays a vital role in the development of age-related cataract and it can be used as a biomarker. Thus, SIRT1 inhibitors can be used in the treatment of age-related cataract disease.

Assessment of Pain Sensitivity in Patients With Chronic Low Back Pain and Association With HTR2A Gene Polymorphism.

OBJECTIVES: This study aims to investigate the association of two common HTR2A gene polymorphisms, rs6313 (102 T/C) and rs6311 (1438 A/G), with chronic low back pain (CLBP) and the pain threshold, disability, and sex differences. PATIENTS AND METHODS: A total of 121 patients (40 males, 81 females; mean age 36.8±9.9 years; range 18 to 50 years) having CLBP and 91 healthy controls (26 males, 65 females; mean age 34.1±10.2 years; range 18 to 55 years) were included. Pressure pain thresholds (PPTs) of all participants were examined with manual algometer in certain sites of their body. RESULTS: The PPTs were all decreased in CLBP patients (p<0.05). Although PPTs were lower in healthy female subjects, there was no sex difference regarding PPTs in CLBP patients (p>0.05). rs6311 polymorphism of HTR2A gene was associated with CLBP (p<0.05). In rs6313 polymorphism, at least one copy of T carriers and in rs6311 polymorphism, at least one copy of G carriers showed higher disability. CONCLUSION: The PPT decreases in CLBP patients similar to other chronic pain conditions without any sex difference. Although rs6311 single nucleotide polymorphism of HTR2A gene was associated with CLBP and rs6313 polymorphism was not, rs6311 might have a protective effect on disability of these patients.

Association of rs11209032 and rs1004819 Polymorphisms in Interleukin-23 Receptor Gene With Ankylosing Spondylitis.

OBJECTIVES: This study aims to investigate the distribution of human leukocyte antigen B27 (HLA-B27) alleles (+/-) and interleukin-23 receptor (IL-23R) gene rs11209032 and rs1004819 polymorphisms among ankylosing spondylitis (AS) patients in a Turkish cohort. PATIENTS AND METHODS: The study sample comprised 106 AS patients (89 males, 18 females; mean age 38.9±10 years; range 19 to 65 years) and 82 healthy controls (70 males, 12 females; mean age 32.15±7.07 years; range 19 to 51 years). Distribution of HLA-B27 alleles (+)/(-) in AS patients were observed by reverse hybridization technique. Genotyping of IL-23R rs11209032 and rs1004819 polymorphisms of AS patients and healthy controls were performed by real time polymerase chain reaction. RESULTS: Of the AS patients, 69 (65.1%) were HLA-B27 positive. Distribution of rs11209032 genotype frequencies in AS group were 31.1% for GG, 50.9% for GA, and 17.9% for AA; while in control group, it was 34.1% for GG, 53.7% for GA, and 12.2% for AA. Distribution of rs1004819 genotype frequencies in AS group were 30.2% for CC, 52.8% for CT, and 17.0% for TT; while in control group, it was 42.7% for CC, 46.3% for CT, and 11.0% for TT. There was no significant difference between AS patients and controls in terms of genotype frequencies of IL-23R gene rs11209032 and rs1004819 polymorphisms. CONCLUSION: No association was found between AS and IL23R rs11209032 and rs1004819 polymorphisms in this Turkish AS cohort.

Association of Alzheimer's Disease With APOE and IL-1α Gene Polymorphisms.

Apolipoprotein E (ApoE) gene polymorphisms are thought to be the most important genetic risk factor in the pathogenesis of late onset and sporadic Alzheimer's disease (AD). Moreover, interleukin-1α (IL-1α) is found to be associated with the pathogenesis of AD. In this research, ∊2, ∊3, and ∊4 polymorphisms of ApoE gene and C889T polymorphism of IL-1α gene were genotyped in patients with AD and controls. Genotyping was performed by real-time polymerase chain reaction. ∊3/∊3 and ∊3/∊4 genotype frequencies were significantly higher in control and case groups, respectively. While ∊3 allele frequencies were significantly higher in the control group, ∊2 and ∊4 allele frequencies were significantly higher among the cases with AD. No difference was found between the groups according to C889T polymorphism of IL-1α. In conclusion, we demonstrated that there was a strong association between ApoE ∊4 allele and AD, while there was no relation with IL-1α C889T polymorphisms for this study.

Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene.

The aim of this study is to investigate the genetic influence of polymorphisms in fat mass and obesity associated (FTO) gene on a sample of obese subjects and controls. Obesity is an epidemic all over the world. Several polymorphisms in the first intron of FTO gene have been associated with common forms of human obesity. In this research rs1421085 and rs9939609 polymorphisms of FTO gene were genotyped in 190 obese patients with a BMI ≥30 kg/m(2) (Body Mass Index) and 97 healthy controls with a BMI of 18.5-24.9. Genotyping of SNPs was performed by real-time polymerase chain reaction. Body composition was established with bioelectric impedance analysis. Waist-to-hip ratio was determined for all participants. There were no significant differences (P > 0.05) between obese cases and controls in terms of genotype frequencies of rs1421085 and rs9939609 polymorphisms in our study. Also there were no significant correlations between genotypes and obesity related (anthropometric-body composition) parameters (P > 0.05).

Association of schizophrenia with T102C (rs6313) and 1438 A/G (rs6311) polymorphisms of HTR2A gene.

OBJECTIVE: The aim of this study is to investigate whether there were any associations between the T102C and 1438 A/G polymorphisms of the 5-HT2A receptor gene and schizophrenia. We conducted a case-control study of the T102C and 1438 A/G polymorphisms in Turkish patients. METHODS: We compared genotypes and allele frequencies of T102C and 1438 A/G polymorphisms of 5-HT2A receptor gene in 102 patients with schizophrenia diagnosed, according to DSM-IV, and 107 healthy controls. Genotyping was performed by real-time polymerase chain reaction. RESULTS: We found no significant association between schizophrenia and genotypic or allele frequencies of HTR2A gene 102T/C (rs6313) and 1438 A/G (6311) polymorphisms. However, comparison of HTR2A gene 102 T/C and 1438 A/G polymorphisms in terms of genotypic and allele frequencies between the two patient groups, with or without a family history of schizophrenia, shows that T- and A-allele frequencies were significantly higher (p < 0.05) in the case group that has a history of schizophrenia in their family. CONCLUSION: In conclusion, our results do not support the hypothesis that the T102C and 1438 A/G polymorphisms in the 5-HT2A receptor gene are associated with schizophrenia, but further studies in a larger sample are needed.