Investigation of Relationship Between Small Noncoding RNA (sncRNA) Expression Levels and Serum Iron, Copper, and Zinc Levels in Clinical Diagnosed Multiple Sclerosis Patients.

In our study, we aimed to investigate the relationship between microRNA (miRNA) expression levels and serum iron (Fe), copper (Cu), and zinc (Zn) levels in Multiple sclerosis (MS) patients. Total RNA was isolated from peripheral venous blood containing ethylenediaminetetraacetic acid (EDTA) of MS patients and controls. Total RNA was labeled with Cy3-CTP fluorescent dye. Hybridization of samples was performed on microarray slides and arrays were scanned. Data argument and bioinformatics analysis were performed. Atomic absorption spectrophotometer method was used to measure serum Fe, Cu, and Zn levels. In our study, in bioinformatics analysis, although differently expressed miRNAs were not detected between 16 MS patients and 16 controls, hsa-miR-744-5p upregulation was detected between 4 MS patients and 4 controls. This may be stem from the patient group consisting of MS patients who have never had an attack for 1 year. Serum iron levels were detected significantly higher in the 16 MS patients compared to the 16 controls. This may be stem from the increase in iron accumulation based on inflammation in MS disease. According to the findings in our study, hsa-miR-744-5p upregulation has been determined as an early diagnostic biomarker for the development together of insulin resistance, diabetes mellitus associated with insulin signaling, and Alzheimer's diseases. Therefore, hsa-miR-744-5p is recommended as an important biomarker for the development together of diabetes mellitus, Alzheimer's disease, and MS disease. In addition, increased serum Fe levels may be suggested as an important biomarker for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and MS disease.

Investigation of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patients with colorectal cancer.

BACKGROUND: The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer. Mateials and Methods. Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method. RESULTS: Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p < 0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p < 0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p < 0.05). CONCLUSION: In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.

Investigation of VEGF and IL-8 Gene Polymorphisms in Patients with Differentiated Thyroid Cancer.

BACKGROUND: Differentiated thyroid carcinomas (DTC) account for most of the thyroid cancers. The emergence of DTC may be affected by various predisposing genetic alterations and environmental factors The aim of this study was to investigate the role of VEGF C936T and IL-8 A251T gene polymorphisms in the pathogenesis and metastasis of differentiated thyroid cancer. METHODS: The study consisted of 101 patients DTC patients and 109 healthy controls. The parameters of the stage of cancer of the DTC patients at the time of diagnosis (TNM) were recorded. DNA was isolated from blood using a DNA isolation kit. VEGF C936T and IL-8 A251T gene polymorphisms were determined using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Distributions of gene polymorphisms were evaluated according to the Hardy-Weinberg principle. RESULTS: The TT genotype from the VEGF C936T genotype distributions was higher in the control group than in the DTC group (p < 0.05). In contrast, the IL-8 A-251T genotype distributions were similar in both groups. No relationship was found between either cytokine gene polymorphism or the DTC stages. The frequency of IL-8 TT was higher in the DTC group with lymph gland metastasis (TT 92%) than in the group without lymph gland metastasis (TT 45.9%) (p < 0.05). CONCLUSIONS: We consider that the VEGF 936 TT genotype may play a protective role in the development of DTC and that the IL-8 A-251 TT genotype may contribute to the DTC lymph node metastasis. Therefore, these genotypes may hold a key to the evaluation of thyroid nodules and the metastasis of DTC.

Relationship Between an Osteoprotegerin Gene Polymorphism and Diabetic Vascular Complications.

BACKGROUND: Osteoprotegerin (OPG), which was recently identified as a vascular marker, is increased in patients with diabetes mellitus (DM). This study evaluated the frequency of the OPG gene single nucleotide A163G polymorphism and its association with diabetic microvascular and macrovascular complications. METHODS: The A163G polymorphism of the OPG gene was assessed in the peripheral blood of 116 patients with type 2 DM and 107 healthy subjects by polymerase chain reaction and restriction fragment length polymorphism. Microvascular and macrovascular complications were evaluated in diabetic patients. RESULTS: Statistical analysis showed no significant difference in distribution of the OPG A163G polymorphism in the diabetic and control groups. Similarly, this polymorphism was not associated with microvascular or macrovascular complications. CONCLUSIONS: This OPG polymorphism does not play a role in the development of microvascular and macrovascular complications in patients with DM.

Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer.

We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy-Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC.

Relationship between cyclin D1 (A870G) gene polymorphism and lung cancer.

The roles of many genes in the pathophysiology of lung cancer have been investigated in different studies. Cyclin D1 (CCND1) gene plays a significant role in the transition from G1 to S phase of the cell cycle and in the phosphorylation of retinoblastoma tumor suppressor protein. In this study, we aimed to identify the relationship between CCND1 A870G gene polymorphism with lung cancer. CCND1 A870G genotypes were determined in 75 patients with lung cancer and in 65 control subjects. DNA was isolated from blood samples and then CCND1 A870G gene polymorphism was identified using PCR and RFLP assay. The distribution of CCND1 A870G polymorphism did not show any significant differences in all lung cancer patients and controls. There was no correlation between CCND1 A870G polymorphism and histopathological findings. However, the AA + AG genotype was significantly higher in metastatic patients, when compared with non-metastatic patients. Thus, the results show that CCND1 gene polymorphism may be a predictor for detecting patients with poor survival who having metastatic disease.

The prognostic significance of p21 and Her-2 gene expression and mutation/polymorphism in patients with gastric adenocarcinoma.

Analyses of gene expression status and genetic polymorphisms are methods to identify novel histopathological prognostic factors. In patients with gastric cancer, some cell cycle regulators p53, p21, p27 and Her-2 oncogene have been proposed as prognostic factors. We aimed to investigate the expression and mutation/polymorphism of p21 and Her-2 and also relationship between that genes status and histopathological factors and prognosis in patients with gastric cancer. Forty-four patients with locally advanced gastric cancer were analyzed in this study from January 2000 to December 2008. Clinicopathological parameters, expression and mutation/polymorphism of p21 and Her-2 results were used to predict disease-free survival and overall survival. The positive expression of p21 and Her-2 was observed in 61.4 % (n = 27) and 9.1 % (n = 4) of all 44 tumors, respectively. p21 gene mutation and Her-2 gene polymorphism were detected in 20 % (n = 11) and 2.3 % (n = 1, II phenotype) of cases, respectively. The negative expression of p21 was correlated significantly with diffuse and undifferential type histologies, whole gastric involvement and positive vascular/neural invasion. The median survival rate of patients with negative expression was significantly poorer than that of patients with positive expression of p21 (17 vs. 27 months, p = 0.01, cox regression). p21 mutation was significantly higher in patients with diffuse (p = 0.03) and undifferential (p = 0.02) type histologies. There was no statistically significant association between histopathological parameters and Her-2 gene polymorphism/expression. The negative expression of p21 correlates with disease survival and may be a poor prognostic factor in patients with resected gastric cancer treated with adjuvant chemotherapy.

G protein mutations in pituitary tumors: a study on Turkish patients.

Activating mutations of the G proteins, Gsalpha (gsp) and Gi2alpha (gip) have been reported in subsets of pituitary tumors. The objective of the study was to assess the frequency of gsp and gip mutations in pituitary tumors from Turkish patients and to investigate the possibility of mutations of protein kinase A catalytic subunit (PKAC) that activates the downstream effectors of adenylyl cyclase. PCR-amplified genomic DNA was analyzed for the presence of mutations in codons 201 and 227 of Gsalpha, codon 179 and 205 of Gi2alpha and codon 196 of PKAC, by single strand conformation polymorphism analysis, allele-specific oligonucleotide hybridization and DNA sequencing. Twenty-two patients from Turkey, 15 females and 7 males were investigated; 7 somatotroph adenomas, 7 clinically non-functioning tumors, 7 prolactinomas and 1 corticotroph adenoma. G protein mutations were identified in 6 of 22 (27.3%) pituitary tumors. Four tumors (3/7 somatotroph adenomas, 43%, 1/7 clinically non-functioning tumor) demonstrated gsp mutations at codon 201 arginine to cysteine and one recurrent somatotroph adenoma demonstrated a mutation of the Gi2alpha gene at codon 193 lysine to arginine. One tumor exhibited a C to T variation in the intervening sequence between codons 179 and 205 of the Gi2alpha gene. No mutations at codon 227 of Gsalpha, codons 179 and 205 of Gi2alpha and codon 196 of the PKAC gene were identified.