Betul Eser

Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease.

The aim of this study was to investigate the association between the polymorphisms of the vitamin D receptor (VDR) and aggrecan genes and degenerative disc disease in young Turkish patients. Aggrecan and VDR proteins are the main components of bone and cartilage. In our study, the polymorphisms of the VDR and aggrecan genes were investigated in a total of 300 individuals regarding disc degeneration and herniation. An association was found in the patients having VDR gene TT, Tt, FF, and Ff genotypes with the protrusion type of disc herniation, whereas the patients having tt and ff genotypes were associated with extrusion/sequestration types of the disease. Also, an association was observed between TT and FF genotypes of the VDR gene and mild forms of disc degeneration; and tt, ff, and Ff genotypes and severe forms of the disease. There was also an association between shorter, normal, and longer alleles of the aggrecan gene and a protrusion type of disc herniation. An association was found between short alleles and multilevel and severe disc degeneration, as well as normal and long alleles and mild disc degeneration. This study revealed that the polymorphisms of the VDR and aggrecan genes are associated with disc degeneration and herniation.

The prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in central serous chorioretinopathy and its association with plasma PAI-1 levels.

Abstract Context: Central serous chorioretinopathy (CSCR) is a poorly understood disease and the choroidal circulation abnormality induced by the plasminogen activator inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are many reports indicating that 4G/5G polymorphism of the PAI-1 gene is a risk factor for several diseases related to the elevated serum levels of PAI-1. Objective: To evaluate the 4G/5G polymorphism of the PAI-1 gene and its association with serum levels of PAI-1 in acute CSCR patients. Materials and methods: Sixty CSCR patients and 50 healthy control patients were included. The PAI-1 4G/5G was genotyped using the polymerase chain reaction–restriction technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent assay. Demographic data consisting of age, sex, body mass index (BMI) as well as genotype disturbances and serum PAI-1 levels were compared between the groups. Statistical significance for differences in the serum PAI-1 levels of each group with different genotypes was also analyzed. Results: The CSCR group consisted of 40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 ± 8.39 years. The control group consisted of 32 male (64%) and 18 female (36%) healthy subjects with a mean age of 45.8 ± 8.39 years. There was no statistically significant difference between the groups in terms of age, sex and BMI. In the CSCR group the genotype frequencies were 4G/4G: 30% (n = 18), 4G/5G: 50% (n = 30), 5G/5G: 20% (n = 12) and in the control group genotype frequencies were 34% (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically significant difference in the distribution of genotypes among the groups (chi-squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1 concentration than the control group (p = 0.001). In both groups the mean plasma PAI-1 concentration did not vary significantly among the different genotypes (p > 0.05). Discussion and conclusion: Although our results demonstrated that the patients with acute CSCR have higher serum PAI-1 concentrations than the controls, no significant difference was found in the genotype disturbances of the PAI-1 gene between the groups. The current study indicates that 4G/5G polymorphism in the promoter of the PAI-1 gene cannot be considered a risk factor for the elevated serum PAI-1 levels and consequent development of CSCR.

NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome

Abstract Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n = 28) or non-obese group (n = 32). NUCB2 was genotyped using the polymerase chain reaction-restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p < 0.001). There was no statistically significant difference in the distribution of NUCB2 genotypes among the groups (p > 0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS.

The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome

Abstract Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.

Evaluation of tool-like receptor-2 and 4 and interleukin-6 gene expressions in Turkish rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a progressive inflammatory disease. Although the etiology and pathogenesis of RA are not known well, genetic and environmental factors are proposed to initiate an autoimmune process. We aimed to investigate mRNA expression levels of Toll-like receptor-2 (TLR-2), TLR-4, and interleukin-6 (IL-6) genes in RA disease. This study was conducted with 50 patients who were diagnosed with RA according to the American College of Rheumatology classification criteria for RA and 50 age-matched healthy control individuals who did not have any joint diseases and autoimmune diseases. We collected whole blood from all participants and analyzed expression of TLR-2, TLR-4, and IL-6 genes at mRNA level using real-time qPCR. TLR-2 expression was detected to increase 3.8-fold and IL-6 expression was detected to increase 6.8-fold in RA patients compared to healthy controls. No difference was found between patient and control groups with regard to TLR-4 expression. Overexpression of TLR-2 and IL-6 may be responsible for RA pathogenesis. Inhibition of both TLR and IL signaling pathways may prevent joint inflammation and destruction.

Two different nucleotide substitutions of APC gene in a family with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome leading to colorectal cancer. This disease appears as a result of germline mutation in adenomatous polyposis coli (APC) gene. The aim of the present study is to report the association between two different nucleotide substitutions detected in a family with FAP. In the proband, p.His1172Gln (c.3516delT) was detected in exon 15 of the APC gene. Furthermore, p.His1172Gln (c.3516delT) and, in addition to this mutation, p.Met1413Val (c.4237 A > G) were detected in exon 15 in both daughters of the proband. However, we believe that single nucleotide change in codon 1413 may be a polymorphic variant and deletion T in codon 1172 of APC gene is associated with FAP, attenuated FAP and extracolonic FAP involvement. Along with common use of genetic tests in the clinical practice, genotype–phenotype correlation may be recognized better and useful for early diagnosis and prevention of familial cancer syndromes.

Prenatal Diagnosis of a De Novo Partial Trisomy 17q Case Associated with Increased Nuchal Translucency, Hypoplastic Left Heart Syndrome, Cerebral Anomalies: Case Report

recorded in spontaneous abortions and but with an extremely low incidence.1 Partial trisomy 17q is rare. Until now, 32 cases of partial trisomy for the distal region of 17q were reported either inherited or de novo.2-8 A derivative chromosome 4 due to partial trisomy of chromosome 17q has never been described, to our knowledge. We demonstrated that the fetus was a carrier of a de novo derivative chromosome 4 arising from partial trisomy 17q. Use of fluorescent in situ hybridization (FISH) analysis permitted the identification of the chromosome 17q breakpoint regions and confirmed the cytogenetic results.

The effects of polymorphisms of death pathway genes and mitochondrial pathway genes in intervertebral disc degeneration

AIM It has been proposed that apoptosis is effective on intervertebral disc degeneration. This study is the first study in which both polymorphisms and expressions of apoptotic genes in patients with intervertebral disc degeneration (IVDD) are evaluated together. The aim of our study is to determine whether polymorphisms and expressions of apoptotic genes involved in both pathways are related with grades of IVDD or not. MATERIAL AND METHODS Blood and tissue samples of 100 patients diagnosed with lumbar disc degeneration were collected. Patients were divided into 2 groups according to their radiological degeneration grades; grade 2 (mild), and grade 3 and 4 (severe). Polymorphisms in Fas (rs 2234767), Bcl-2 (rs 1801018) and Bax (rs 4645878) genes were determined with real-time PCR. Expressions of these genes were analyzed immunohistochemically following histological degeneration scoring. RESULTS Whereas no relationship was found among polymorphisms of Fas and Bax genes and their expressions, we have determined a relationship among GG genotype of Bcl-2 and their expressions. Additionally, the ratio of Bax-positive cells was related with IVDD grades. Moreover, radiological degeneration grades were compatible with histological degeneration scores. CONCLUSION GG genotype of Bcl-2 gene may influence the level of its expression and may be effective on the development of IVDD. Additionally, expression of Bax gene may be related with different grades of IVDD.

Increased Expression of Matrix Metalloproteinases in Ligamentum Flavum Hypertrophy of the Patients with Lumbar Spinal Stenosis

Abstract This paper shows an investigation of the expressions of MMP-3,-13 and their polymorphisms in patients with lumbar spinal stenosis (LSS). Hypertrophied LF tissues and peripheral bloods were obtained from 50 patients with LSS. The expressions of MMP-3,-13 and their polymorphisms were analyzed. No relationship was found between thickness of LFs and MMP-3,-13 genotypes. LF tissues were divided to three groups as grade 1, 2 and 3. Rich elastic fibrils were observed in grade 1. Elastic fibers and elastin/collagen rates decreased in grade 2-3 and 4, and collagen fibers increased and presented a cystic degeneration. MMP-3 immunopositive cells were higher than MMP-13. A correlation between LF thicknesses and MMP-3 was detected. Both MMP-3, -13 were expressed (MMP-3 in higher quantities) in high grade hypertrophied LF. The researchers expect that this paper would provide a better understanding of the pathogenesis of LF hypertrophy and lead to therapeutic alternatives for LSS patients.