Immunohistochemical and molecular evaluation of TUSC2 expression in breast cancer.

OBJECTIVE: Tumor suppressor candidate 2 has shown to be deleted in lung, colon, and bladder cancer types. In the present study, we aimed to investigate the expression of TUSC2 in breast cancer. MATERIALS AND METHODS: A total of thirty patients with breast cancer were included in the study. Normal and tumor tissue samples from fresh mastectomy materials were stored at -80 C until the number of cases was completed for gene expression analysis. Histopathological examination was carried out with routine hematoxylin & eosin method. TUSC2 staining was performed for immunohistochemical analysis. RESULTS: The tumors of thirteen patients were Luminal A, fourteen patients were Luminal B, one patient was cerbB2(+), and tumors of two patients were triple-negative. Ki67 proliferation index was less than 14% in fifteen cases and tumor size was less than 2 cm in seven cases. Lymphovascular invasion and lymph node metastasis were present in thirteen cases. Statistically, TUSC2 expression significantly decreased or was lost in breast tumor tissues compared to normal tissues (p < 0.0001). TUSC2 expression decreased as the Ki67 proliferation index increased (p = 0.0003), and TUSC2 expression decreased as tumor size increased (p = 0.0483). The loss or decrease in the TUSC2 expression was significant as the tumor grade increased (p = 0.3740). Gene expression analysis correlated with immunohistochemistry results. CONCLUSION: The results of the present study demonstrated a decrease or loss of TUSC2 expression in breast cancer tissue compared to normal tissue. A correlation was found between TUSC2 expression and Ki67 proliferation index and tumor size.

Evaluation of mTOR Activity in COPD Patients with Emphysema.

OBJECTIVE: To evaluate the function of the mammalian target of the rapamycin (mTOR) pathway in chronic obstructive pulmonary disease (COPD) patients with emphysema. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Pulmonology, Mugla Training and Research Hospital, Turkey, from January to March 2022. METHODOLOGY: Thirty COPD patients and thirty healthy volunteers were included. Demographic data, pack-year of cigarette, spirometric values, and emphysema percentage (calculated with CT scan) were recorded. mTOR, raptor, and deptor were measured with ELISA method. Statistical significance was accepted as p<0.05. RESULTS: The mean value of mTOR in the COPD group was 3.48±2.01 ng/ml and it was significantly higher than the control (1.51±0.44 ng/ml). The mTOR was positively correlated with MMRC, annual exacerbation rate, emphysema percentage, and pack/year of cigarette and negatively correlated with SpO2 and FEV1. The significant relationship was found with only emphysema (B=0.067, SE=0.020, 95% CI=0.027-0.107, p=0.002). The cut-off value of mTOR for COPD was found as 1.815 ng/ml (sensivity=77%). CONCLUSION: Overexpression of mTOR and its signalling proteins have a significant role in emphysema development. Reduction of mTOR expression/activity might be helpful to control dyspnea severity, number of exacerbations, loss of FEV1, and progression of emphysema. KEY WORDS: COPD, Emphysema, mTOR.

In Vitro Effects of Propofol on Cytotoxic, Apoptotic and PI3K-Akt Signaling Pathway Genes on Brain Cancer Cells.

AIM: The study aimed to determine the cytotoxic and apoptotic effect of propofol on glioma cells. BACKGROUND: Propofol [2,6-diisopropylphenol] is a commonly used intravenous anesthetic. Propofol is known to have a mechanism of action on the PI3K-AKT pathway. OBJECTIVE: This study aimed to evaluate the effect of propofol on the proliferation and apoptosis of human glioma cells, as well as to investigate changes in expression levels of the PI3K-AKT signaling pathway genes. MATERIALS AND METHODS: The cytotoxic effect of propofol on the U-87 MG cell line was determined by WST-1 method. Annexin V-FITC and Mitoprobe JC-1 assay were used to measure apoptosis by flow cytometry. The expression levels of genes in the PI3K-AKT signaling pathway were investigated by qRT-PCR. RESULTS: We have shown that propofol induced apoptosis in U-87 MG cells by 17.1 fold compared to the untreated control. Furthermore, significant differences were found in the expression levels of the PI3K-AKT signaling pathway genes. CONCLUSION: As a result of our study, it was found that propofol caused differences in expression levels of PI3K-AKT signaling pathway genes and it was suggested that these differences may be related to apoptosis induction.

The role of Wnt pathway antagonists in early-stage lung adenocarcinoma.

PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.

Exploration of Potential miRNA Biomarkers and Prediction for Ovarian Cancer Using Artificial Intelligence.

Ovarian cancer is the second most dangerous gynecologic cancer with a high mortality rate. The classification of gene expression data from high-dimensional and small-sample gene expression data is a challenging task. The discovery of miRNAs, a small non-coding RNA with 18-25 nucleotides in length that regulates gene expression, has revealed the existence of a new array for regulation of genes and has been reported as playing a serious role in cancer. By using LASSO and Elastic Net as embedded algorithms of feature selection techniques, the present study identified 10 miRNAs that were regulated in ovarian serum cancer samples compared to non-cancer samples in public available dataset GSE106817: hsa-miR-5100, hsa-miR-6800-5p, hsa-miR-1233-5p, hsa-miR-4532, hsa-miR-4783-3p, hsa-miR-4787-3p, hsa-miR-1228-5p, hsa-miR-1290, hsa-miR-3184-5p, and hsa-miR-320b. Further, we implemented state-of-the-art machine learning classifiers, such as logistic regression, random forest, artificial neural network, XGBoost, and decision trees to build clinical prediction models. Next, the diagnostic performance of these models with identified miRNAs was evaluated in the internal (GSE106817) and external validation dataset (GSE113486) by ROC analysis. The results showed that first four prediction models consistently yielded an AUC of 100%. Our findings provide significant evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

The role of adropin, salusin-α, netrin-1, and nesfatin-1 in endometriosis and their association with insulin resistance

Objective: The pathogenesis of endometriosis has not been clearly explained. Inflammatory factors of ectopic implantation and the growth of ectopic endometrial cells have been subjects of major interest. The number of studies evaluating salusin-α and nesfatin-1 markers in patients with endometriosis is limited. No studies have evaluated the levels of anti-inflammatory markers for adropin and netrin-1 in patients with endometriosis. This study investigates how some important inflammatory regulatory markers in the inflammatory process affect the pathogenesis of endometriosis and determines whether any relationship exists between serum levels of these parameters and endometriosis and insulin resistance. Materials and Methods: This prospective study included 73 patients with endometriosis diagnosed histopathologically after laparoscopic surgery and 75 healthy controls. Serum adropin, salusin-α, netrin-1, and nesfatin-1 levels and homeostatic model assessment of insulin resistance (HOMA-IR) values of the participants were measured. Results: The endometriosis group had significantly lower nesfatin-1 levels than the control group (3.0±0.53 vs 9.5±0.94, p=0.005). Between the patient and control groups, there was no difference regarding serum adropin, salusin-α, and netrin-1 levels (p=0.36, p=0.34, p=0.75, respectively). Nesfatin-1 had a significant positive correlation with adropin, salusin-α, and netrin-1 (r=0.563, p<0.01; r=0.738, p<0.01; r=0.700, p<0.01, respectively), but had a negative correlation with fasting blood glucose (r=-0.343, p<0.05). HOMA-IR values were comparable between both groups. Conclusion: The lower nesfatin-1 levels leading to increased inflammatory pathway activity in patients with endometriosis might play a role in endometriosis pathogenesis. Without causing systemic insulin resistance, decreased nesfatin-1 might contribute to endometriosis pathogenesis locally by leading to the reduced insulin susceptibility of endometriosis cells.

Gene variants and serum levels of synaptic vesicle and presynaptic plasma membrane proteins in alcohol dependence and their relationship with impulsivity and temperament

ABSTRACT Background: Exocytosis-related gene variants have been suggested to be associated with externalizing behaviors. Objective: This study aimed to examine VAMP2 26 bp Ins/Del, synaptotagmin XI (Syt11) rs3820594 and 33-bp promoter, Syntaxin 1A (Syn-1A) rs1569061 and SNAP-25 rs1051312 and rs3746544 polymorphisms, their serum levels and their relationship with impulsivity, temperament in individuals with alcohol dependence (AD) and healthy controls (HC). Methods: The study included 107 individuals with AD and 104 HCs. Single-nucleotide polymorphisms (SNPs) were studied with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and serum levels with ELISA. Michigan Alcohol Screening Test (MAST), Barratt Impulsiveness Scale-11 (BIS-11) and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) were applied. Results: Syn-1A rs1569061 C allele polymorphism was significantly higher in AD group. Syn-1A rs1569061 C allele was associated with 1.5 times increased risk of AD. All serum levels were significantly higher in the HC group. There was a relationship between Syn-1A rs1569061 polymorphism and BIS-11 motor impulsiveness in the AD group; Syt11 rs3820594 polymorphism and BIS-11 total, TEMPS-A depressive, hyperthymia in the HC group. Discussion: In our study, gene variants and serum levels of synaptic vesicle and presynaptic plasma membrane proteins were related to AD, impulsivity and temperament.

SMAD2, SMAD3 and TGF-ß GENE expressions in women suffering from urge urinary incontinence and pelvic organ prolapse.

We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the uterosacral ligament (USL) of patients with concomitant pelvic organ prolapse (POP) and urgency urinary incontinence (UUI) to illuminate the pathophysiology of UUI. The TGF-ß pathway is involved in collagen synthesis and degradation. The Transforming Growth Family-ß (TGF-ß) superfamily has essential intracellular signaling components, such as newly identified SMAD family members. We evaluated the changes in the levels of TGF-ß and SMAD gene and protein expression in the USL of patients with concomitant pelvic organ prolapse (POP) and UUI. This study included 10 patients who had been diagnosed with POP and UUI in the study group and 14 asymptomatic women without complaints of POP and UUI in the control group. Biopsy samples were collected from bilateral USL tissues during vaginal or abdominal hysterectomy. Total RNA was extracted from USL tissue and analyzed by qPCR. The protein expression levels were also analyzed with ELISA. In UUI patients, SMAD3 and TGF-ß1 gene expression levels significantly decreased compared to the control patients (p = 0.008 and p = 0.006, respectively). SMAD2 mRNA levels did not differ between the study and control groups (p = 0.139). No differences was found in the levels of SMAD2, SMAD3, and TGF-ß1 protein expression between the two groups. The reduction in the gene and protein expression levels of SMAD3 and TGF-ß1 in women with UUI and lax uterosacral ligaments may indicate a causal link.Clinical trial registration: NCT04525105.

Identifying Potential miRNA Biomarkers for Gastric Cancer Diagnosis Using Machine Learning Variable Selection Approach.

Aim: This study aimed to accurately identification of potential miRNAs for gastric cancer (GC) diagnosis at the early stages of the disease. Methods: We used GSE106817 data with 2,566 miRNAs to train the machine learning models. We used the Boruta machine learning variable selection approach to identify the strong miRNAs associated with GC in the training sample. We then validated the prediction models in the independent sample GSE113486 data. Finally, an ontological analysis was done on identified miRNAs to eliciting the relevant relationships. Results: Of those 2,874 patients in the training the model, there were 115 (4%) patients with GC. Boruta identified 30 miRNAs as potential biomarkers for GC diagnosis and hsa-miR-1343-3p was at the highest ranking. All of the machine learning algorithms showed that using hsa-miR-1343-3p as a biomarker, GC can be predicted with very high precision (AUC; 100%, sensitivity; 100%, specificity; 100% ROC; 100%, Kappa; 100) using with the cut-off point of 8.2 for hsa-miR-1343-3p. Also, ontological analysis of 30 identified miRNAs approved their strong relationship with cancer associated genes and molecular events. Conclusion: The hsa-miR-1343-3p could be introduced as a valuable target for studies on the GC diagnosis using reliable biomarkers.

Assessment of COL1A1 and MMP9 expression in patients with dermatochalasis.

PURPOSE: Dermatochalasis is a clinical condition characterized by loss of elasticity of eyelid skin and soft tissue, which typically affects the elderly population. The aim of this study is to investigate the mRNA expression levels of collagen type 1 alpha 1 (COL1A1) and matrix metalloproteinase-9 (MMP9) genes in dermatochalasis tissue. METHODS: The study group consisted of 15 patients who underwent upper eyelid blepharoplasty and were above 40 years old. The patients in our control group were divided into two subgroups according to their ages. Fourteen patients who were under 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the young control group. Sixteen patients who were older than 40 years old and had anterior blepharoptosis surgery for blepharoptosis were designed as the old control group. The patients in the dermatochalasis group were also evaluated according to their smoking status. Surgical tissue specimens were analyzed for COL1A1 and MMP9 mRNA gene expression levels by using real-time polymerase chain reaction. RESULTS: COL1A1 and MMP9 mRNA gene expression levels were not statistically different between the groups (p = 0.247; p = 0.052, respectively). When compared in means of the smoking habit, smokers in the dermatochalasis group exhibited higher COL1A1 mRNA expression levels when compared to nonsmokers (p = 0.008). MMP9 gene expression levels of smokers exhibited almost statistically higher levels but at the limit when compared to nonsmokers (p = 0.05). CONCLUSIONS: This study represents a preliminary study to detect the tissue changes at a molecular level in dermatochalasis, which is known to be related to connective tissue pathology. Collagen and MMPs are essential components of the extracellular matrix, and smoking might affect their gene expression. Further prospective studies on these regulatory genes and encoded protein levels with a larger group of patients may provide particular contribution to explaining the pathophysiology of dermatochalasis.

Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model.

BACKGROUND & OBJECTIVES: Vaginal atrophy is characterized by thinning of vaginal epithelial layers and decreased local blood flow. We aimed to evaluate the regenerative effects of Adipose derived mesenchymal stem cells (ADMSC) and Bone marrow derived mesenchymal stem cells (BMDSC) on vaginal atrophy in rat menopause model. MATERIALS AND METHODS: Rats were randomly divided into 4 (four) groups: sham, control, ADMSC, BMDSC. Vaginal epithelial thickness, structure of the lamina propria, blood vessels in the lamina propria, collagen deposition, and muscle structure were evaluated. Anti ER α, VEGF, VEGFR 1, Bax and bcl-2 antibodies were analyzed. Beta actin gene was used as endogenous control. Genetical differences among the groups were compared by using Kruskal Wallis and Mann Whitney U test. p < 0.05 was regarded as statistically significant. RESULTS: Epithelial thickness of ADMSC group was higher than control group, but less than sham group Epithelial thickness of BMDSC group was less than sham group. Lamina propria and muscle tissue of ADMSC and BMDSC groups were found to be similar to sham group. VEGFR-1, VEGF, Bax and ER-α staining levels were higher in ADMSC and BMDSC groups than control group. ADMSC group stained stronger with VEGFR-1 and VEGF than BMDSC group. Bcl-2 staining level was increased in ADMSC applied group. No statistically significant difference was detected in Bax and Bcl-2 genes and Bax-/Bcl-2 ratio. CONCLUSIONS: Although genetic expression might have ended and could not be significantly demonstrated, histological and immunohistochemical results favor ADMSC application in vaginal atrophy rather than BMDSC.

Diagnostic Value of MiR-125b as a Potential Biomarker for Stage I Lung Adenocarcinoma.

BACKGROUND: We aimed at exploring biological functions of differentially expressed miRNAs during carcinogenesis, to identify miRNAs dysegulations involved in DNA repair mechanisms, and to evaluate potential of miRNAs as prognostic and diagnostic biomarkers for early lung adenocarcinomas (LAC). METHODS: We obtained 21 LAC and paired adjacent normal formalin-fixed, paraffinembedded lung tissues from patients who underwent curative resection for stage I LAC. We compared expression levels of eight miRNAs involved in the DNA repair mechanism between LAC and adjacent tissues. RESULTS: Expressions of Hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-125a-3p, hsa-miR- 125b-5p, hsa-miR-155-5p, and hsa-let-7a-5p were significantly up-regulated in stage I LAC tissues compared with those in the adjacent tissues. In addition, expressions of hsa-mir-9-5p, hsa-mir-24-3p, hsa-mir-125a-3p, hsa-mir-125b-5p, and hsa-mir-155-5p were significantly up-regulated in stage Ia LAC tissues, whereas expressions of hsa-mir- 125a-3p and hsa-mir-125b-5p were significantly up-regulated in stage Ib LAC tissues. Receiver operating characteristic (ROC) analysis revealed that AUROC of hsa-mir-125b- 5p was 0.875 (P < 0.001). CONCLUSION: Expression of hsa-mir-125b-5p could be used to distinguish LAC from adjacent tissues. Our result suggests that hsa-mir125b-5p can be a prognostic and diagnostic biomarker for LAC.

G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk.

The G-protein-coupled estrogen receptor (GPR30, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants' leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer's exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population.

GPR30 Gene Polymorphisms Are Associated with Gynecomastia Risk in Adolescents.

AIM: The G protein-coupled receptor, GPR30, which is a third estrogen receptor, has been shown to mediate estrogenic effects on the essential features of human breast cancer cells. The aim of this study was to evaluate the association between GPR30 single nucleotide polymorphisms and gynecomastia in males. METHODS: This study included 109 male adolescents with gynecomastia and 104 controls. Follicle stimulating hormone, luteinizing hormone, total testosterone, estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and prolactin levels were measured. DNA was extracted from whole blood using a GeneJET Genomic DNA purification kit. The genotypes of the GPR30 gene (rs3808350, rs3808351 and rs11544331) were studied using a tetra-primer ARMS (amplification refractory mutation system) PCR approach. RESULTS: The median E2 (11.80 vs. 16.86 IU/l, p < 0.001) and DHEAS levels (116.8 vs. 146.5 µg/dl, p = 0.044) were higher in the gynecomastia group. The G allele of rs3808350 and the A allele of rs3808351 were frequently observed in patients with gynecomastia. Gynecomastia was more common in patients with the GG genotype of rs3808350 and in patients with the AA genotype of rs3808351. CONCLUSIONS: Our results suggest that increased E2 levels, the G allele of rs3808350 and the A allele of rs3808351 might explain why certain adolescents are affected by gynecomastia.

Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent.

OBJECTIVE: Gynecomastia is a benign breast enlargement in males that affects approximately one-third of adolescents. The exact mechanism is not fully understood; however, it has been proposed that estrogen receptors and aromatase enzyme activity may play important roles in the pathogenesis of gynecomastia. While many studies have reported that aromatase enzyme (CYP19) gene polymorphism is associated with gynecomastia, only one study has shown a relationship between estrogen receptor (ER) alpha and beta gene polymorphism and gynecomastia. Thus, the aim of this study was to evaluate the relationships between CYP19 (rs2414096), ER alpha (rs2234693), ER beta (rs4986938), leptin (rs7799039), and leptin receptor (rs1137101) gene polymorphisms and gynecomastia. METHODS: This study included 107 male adolescents with gynecomastia and 97 controls. Total serum testosterone (T) and estradiol (E2) levels were measured, and DNA was extracted from whole blood using the PCR-RFLP technique. The polymorphic distributions of CYP19, ER alpha, ER beta, leptin and leptin receptor genes were compared. RESULTS: The median E2 level was 12.41 (5.00-65.40) pg/ml in the control group and 16.86 (2.58-78.47) pg/ml in the study group (p<0.001). The median T level was 2.19 (0.04-7.04) ng/ml in the control group and 1.46 (0.13-12.02) ng/ml in the study group (p=0.714). There was a significant relationship between gynecomastia and leptin receptor rs1137101 (p=0.002) and ER beta receptor rs4986938 gene polymorphisms (p=0.002). CONCLUSIONS: According to our results, increased E2 level and ER beta gene rs4986938 polymorphism might explain why some adolescents have gynecomastia. Leptin receptor gene rs1137101 polymorphism might affect susceptibility to gynecomastia.

Sirtuin gene polymorphisms are associated with chronic obstructive pulmonary disease in patients in Mugla province.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an irreversible progressive chronic inflammatory disease that causes shortness of breath in consequence of a decrease in pulmonary functions. The pulmonary inflammatory pathogenesis is multifactorial. We have too little up-to-date information about the relation between COPD and genetics. In our study, the relation with the SIRT1 gene's mononucleotide polymorphisms (SNP) rs7895833, rs7069102 and rs2273773 was analyzed through various laboratory data. MATERIAL AND METHODS: One hundred COPD patients from the archive records of the Chest Diseases Department of Mugla Sitki Kocman University Medical Faculty were included in the study. A control group was constituted from 100 healthy individuals who live in the same geographical region. The SIRT1 genotypes for these patients were determined using polymerase chain reaction (PCR) and confronting two-pair primers (CTPP) methods. The SIRT1 gene polymorphisms rs7895833, rs7069102 and rs2273773 were analyzed. GG, AG, AA genotypes and G and A alleles of rs7895833, TT, TC, CC genotypes and T and C alleles of rs2273773, and CC, CG, GG genotypes and C and G alleles of rs7069102 were examined. The data in both groups were compared. CONCLUSIONS: A significant difference between GG, AG and AA genotypes of rs7895833 was found. Especially, the AG genotype was observed more in the group with COPD, with a significant difference. A significant difference between TT, TC and CC genotypes of rs2273773 was found. There was a significant difference between two groups with regards to C and G alleles of rs7069102. A significant difference was not found between the groups with regards to G and A alleles of rs7895833. A difference was not found for both groups between T and C alleles of rs2273773. It shows that these polymorphisms of the SIRT1 gene may be associated with COPD.

The association of FOXO3A gene polymorphisms with serum FOXO3A levels and oxidative stress markers in vitiligo patients.

Vitiligo is an acquired epidermal pigment loss of the skin. Oxidative stress is one of the major theories in the pathophysiology of vitiligo. FOXO3A is the forkhead members of the class O (FOXO) transcription factors, and plays an important role in cell cycle regulation, apoptosis, oxidative stress, and DNA repair. The aim of our study was to investigate FOXO3A gene polymorphisms and FOXO3A protein levels, activities of superoxide dismutase (SOD) and catalase antioxidant enzymes in vitiligo patients and healthy controls. Moreover, the level of plasma advanced oxidation protein products (AOPP) in subjects was evaluated to understand the possible role of protein oxidation in disease etiology. Study groups included 82 vitiligo patients and 81 unrelated healthy controls. FOXO3A polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism method. FOXO3A levels and catalase activity were measured by ELISA whereas AOPP levels and SOD activity was measured by spectrophotometric analysis. We found a significant relationship between rs4946936 polymorphism of FOXO3A gene and vitiligo/active vitiligo patients (p=0.017; p=0.019 respectively), but not for rs2253310 (p>0.05). SOD activity and AOPP levels of vitiligo patient were increased compared with control group, whereas FOXO3A levels and catalase enzyme activity of vitiligo patient were decreased compared with control group (p<0.05). Our study indicates that rs4946936 of FOXO3A gene may associate susceptibility of vitiligo, especially active vitiligo. Moreover, our results confirm that oxidative stress may play a role in the pathophysiology of vitiligo. Further studies with larger samples are required to elucidate the role of FOXO3A in vitiligo.

Cytokine polymorphism in patients with migraine: some suggestive clues of migraine and inflammation.

OBJECTIVE: There are contrasting results obtained in migraineurs concerning the levels and the role of both pro-inflammatory and anti-inflammatory cytokines. In this study, the association of the occurrence and clinical characteristics of migraine with the polymorphisms of tumor necrosis factor alpha (TNF-alpha) -308 G/A (rs1800629), interleukin-1alpha (IL-1alpha) +4845 G/T (rs17561), IL-1beta+3953 C/T (rs1143634) and interleukin-1 receptor antagonist variable number tandem repeat (IL-1RA VNTR) genes were studied. We also investigated the genetic linkage between these genes. DESIGN, SETTING, PATIENTS: Sixty-seven patients with migraine without aura (MwoA) and 96 unrelated, age- and sex-matched migraine-free, healthy control subjects from the same geographic area were investigated. RESULTS: We observed significant differences in the genotypic distribution of the TNF-alpha-308 G/A and IL-1beta+3953 C/T polymorphism for migraineurs compared with controls (P = 0.004). Frequency of the TNF-alpha-308 GG genotype was higher in the control group than MwoA group (82.1% vs 55.2%). Differences in the distribution of the allele frequencies were also observed, being the TNF-alpha-308 G allele overrepresented in control group and TNF-alpha-308 A allele in MwoA group. In addition, there was a significant increase of the IL-1beta+3953 T allele in MwoA cases compared with controls (P = 0.004). CONCLUSIONS: In conclusion, the present results indicate the possible contribution of TNF-alpha and IL-1beta gene polymorphisms to migraine headache generation in MwoA patients.