Sema Inanir

Association between sequence variations of the Mediterranean fever gene and fibromyalgia syndrome in a cohort of Turkish patients

OBJECTIVE Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Genetic risk factors are known to contribute to the etiology of the syndrome. Clinical features show that FMS and familial Mediterranean fever (FMF) have some overlapping symptoms. Mediterranean fever (MEFV) gene has already been identified as being responsible for FMF. The aim of this study was to explore the frequency and clinical significance of missense mutations and a common polymorphism of MEFV gene in a cohort of Turkish patients with FMS. METHODS The study included 187 patients with FMS and 190 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses for the five MEFV gene mutations (M694V, M680I, V726A, E148Q and P369S) and one polymorphism (R202Q). RESULTS There were statistically significant differences of the MEFV gene mutation carrier rates and allele frequencies between FMS patients and healthy controls (p=0.002, OR: 2.3, 95% CI: 1.35-4.16 and p=0.003, OR: 2.2, 95% CI: 1.28-3.75, respectively). There was also a significant difference between MEFV mutation carriers and non-carriers with respect to the clinical characteristic of morning fatigue (p=0.045). The genotype and allele frequencies of R202Q polymorphism of MEFV gene showed statistically significant differences between FMS patients and healthy controls (p<0.0001 and p<0.0001, respectively) and especially the homozygous AA genotype was significantly higher in FMS patients than in healthy controls (p=0.0003; OR: 7.43, 95% CI: 2.14-39.75). While 13 of the 44 FMS patients with MEFV mutation had R202Q polymorphism, none of the 22 controls with MEFV mutation had R202Q polymorphism. Stratification analysis according to clinical features for this disease reveals that morning fatigue and irritable bowel syndrome had associations with R202Q polymorphism (p=0.022 and p=0.031 respectively). CONCLUSION The results of this study suggest that MEFV gene mutations and polymorphism are positively associated with predisposition to develop FMS. Further studies with larger populations will be required to confirm these findings.

Association between fibromyalgia syndrome and polymorphism of the IL-4 gene in a Turkish population.

PURPOSE Fibromyalgia (FM) syndrome is a form of non-articular rheumatism characterized by long term and widespread musculoskeletal pain, morning stiffness, sleep disturbance, paresthesia, and pressure hyperalgesia at characteristic sites, called soft tissue tender points. The etiology of FM is still obscure. Genetic factors may predispose individuals to FM. Cytokines may play a role in the pathophysiology of FM. The aim of this study was to investigate the interleukin-4 (IL-4) 70 bp VNTR variations in Turkish patients with FM and evaluate if there was an association with clinical features, especially between these polymorphisms. METHODS The study included 300 patients with FM and 270 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) for the IL-4 gene 70 bp VNTR polymorphisms. RESULTS There was statistically significant difference between the groups with respect to IL-4 genotype distribution and allele frequencies (p<0.0001). The homozygous P1P1 genotype and P1 allele were significantly higher in FM patients than in healthy controls (p=0.04; OR: 3.25, 95% CI: 1-10, p<0.0001; OR:4.84, 95% CI:3-7.7). There was not any difference between the groups respect to IL-4 genotype distribution and allele frequencies (p>0.05) and clinical characteristics. CONCLUSION Our findings suggest that there is an association of IL-4 gene 70 bp VNTR polymorphism with susceptibility of a person for development of FM. As a result, further studies are necessary to determine whether IL-4 may be a genetic marker for FM in the Turkish population.

Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome

OBJECTIVE Fibromyalgia syndrome (FM) is a common disease characterized by generalized body pain, sensitivity in certain physical areas (sensitive points), lowered pain threshold, sleep disorder, and fatigue. The study aimed to determine the effects ACE I/D and MTHFR C677T gene polymorphisms in Turkish patients with FM and evaluate if there was an association with clinical features. METHODS This study included 200 FM patients and 190 healthy controls recruited from the department of Physical Medicine and Rehabilitation at Gaziosmanpasa University in Tokat, Turkey. ACE I/D polymorphism genotypes were determined by using polymerase chain reaction (PCR) by specific primers. The MTHFR C677T mutation was analyzed by PCR-based restriction fragment length polymorphism (RFLP) methods. RESULTS We found a statistically significant relation between ACE polymorphism and FM (p<0.001, OR: 1.71, 95% CI: 1.28-2.27). However, this was not the case for ACE polymorphism and the clinical characteristics of the disease. There was also no statistically significant relation between MTHFR C677T mutation and FMS (p>0.05, OR: 1.20, 95% CI: 0.82-1.78), but dry eye and feeling of stiffness which are among the clinical characteristics of FMS were significantly related with MTHFR C677T mutation (p<0.05). CONCLUSION Our findings showed that there are associations of ACE I/D polymorphism with susceptibility of a person for development of fibromyalgia syndrome. Also, it is determined an association between MTHFR C677T polymorphism and feeling of stiffness and dry eye which are among the clinical characteristics of FM. Our study is the first report of ACE I/D and MTHFR C677T polymorphisms in fibromyalgia syndrome.

Clinical symptoms in fibromyalgia are associated to catechol-O-methyltransferase (COMT) gene Val158Met polymorphism.

Abstract 1. Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. The aim of this study was to explore the frequency and clinical significance of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism in a large cohort of Turkish patients with FMS. 2. The study included 379 FMS patients and 290 controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. 3. The genotype frequencies of Val158Met polymorphism showed a small difference between FMS patients and healthy controls (p = 0.047), however, the Met/Met genotype was significantly higher in FMS patients than healthy controls (p = 0.016). No difference was observed for allele frequencies between two groups. Stratification analysis according to clinical features for this disease reveals that weight, FMS Impact Questionnaire score, algometry and Raynaud’s syndrome, were detected to have statistically significant associations with Val158Met polymorphism (p = 0.037, p = 0.042, p = 0.039 and p = 0.033, respectively). Pain sensitivity, measured by algometry, was statistically higher in patients with Met/Met genotype than the patients with Val/Val and Val/Met genotypes (p = 0.017). 4. The results of this study suggested that COMT gene Val158Met polymorphism is positively associated with FMS and play a relevant role in the clinical symptoms of the disease.

Is There a Link Between Obstructive Sleep Apnea Syndrome and Fibromyalgia Syndrome

OBJECTIVES Fibromyalgia syndrome (FMS) is characterized by complaints of chronic musculoskeletal pain, fatigue, and difficulty in falling asleep. Obstructive sleep apnea syndrome (OSAS) is associated with symptoms, such as morning fatigueness and unrefreshing sleep. We aimed to investigate the presence of OSAS and objectively demonstrate changes in sleep pattern in patients with FMS. MATERIAL AND METHODS Polysomnographic investigations were performed on 24 patients with FMS. Patients were divided into two groups: patients with and without OSAS (Group 1 and Group 2, respectively). A total of 40 patients without FMS who presented to the sleep disorders polyclinic with an initial diagnosis of OSAS were included in Group 3. Based on their apnea hypopnea index (AHI), OSAS in the patients were categorized as mild (AHI, 5-15), moderate (30), or severe (>30). RESULTS OSAS was detected in 50% of patients with FMS. The most prominent clinical findings were morning fatigue and sleep disorder, which were similar in three groups. In polysomnography (PSG) evaluation, patients with FMS had mild (33%), moderate (25%), and severe (42%) OSAS. In correlation analyses, negative correlations were observed between fibromyalgia impact questionnaire (FIQ) and mean oxygen saturation, visual analogue scale (VAS), and minimum oxygen saturation, whereas a positive correlation was found between FIQ and desaturation times in patients with FMS. CONCLUSION Detection of OSAS in 50% of the patients with FMS, and similar rates of complaints of sleep disorder and morning fatigue of OSAS and FMS cases are important results. Detection of correlation between the severity of hypoxemia and FIQ and VAS scores are significant because it signifies the contribution of increased tissue hypoxemia to the deterioration of clinical status. Diagnosis and treatment of OSAS associated with FMS are important because of their favorable contributions to the improvement of the clinical picture of FMS.

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Background Major depressive disorder (MDD) is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE) has an important role in renin-angiotensin system (RAS) and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D) polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

The Antipsychotic Effects of Omega-3 Fatty Acids in Rats

Background:In humans, omega-3 fatty acids are necessary for cell membranes, brain function and nerve transmission continuation. When animals are exposed to a new environment—or as a result of an apomorphine application that creates an agonistic effect on D1 and D2 receptors—they display behavioral reactions like rearing and stereotypy. This study aims to reveal the possible antipsychotic and oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a conventional antipsychotic drug, through evaluating the novelty-induced rearing and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and glutathione levels in rats. Methods:Twenty-eight, adult, male, Wistar rats were used in the study. Briefly, 4 groups of rats (n = 7) were administered docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1 mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was administered to each rat. After the apomorphine administration, rats were observed for stereotypic behavior. Results:This study shows that omega-3 fatty acids, “similar to antipsychotics,” reversed the psychotic like effects, increase of oxidants and decrease of antioxidants that are composed experimentally in rats. Conclusions:The application of omega-3 fatty acids has antipsychotic effects and causes an oxidative imbalance. This study adds new evidence to the current literature regarding the possible antipsychotic effects of omega-3 fatty acids.

Agomelatine Protection in an LPS-Induced Psychosis-Relevant Behavior Model.

Background The aim of this study was to investigate the effect of agomelatine in a psychosis-relevant behavior model. Material/Methods We used 18 adult male Wistar rats in this study. Twelve rats given LPS for endotoxemia were randomly divided into 2 groups (n=6). Group I was treated with 1 mL/kg 0.9% NaCl i.p. and Group II was treated with 40 mg/kg agomelatine. Six normal rats served as the control group and were not given LPS for endotoxemia. Cylindrical steel cages containing vertical and horizontal metal bars with top cover were used. Rats were put in these cages for the purpose of orientation for 10 min. Apomorphine was given to rats removed from cages, and then they were immediately put back in the cages for the purpose of observing stereotyped conduct. Brain HVA levels and plasma TNF-α levels were evaluated in tissue homogenates using ELISA. The proportion of malondialdehyde (MDA) was measured in samples taken from plasma for detection of lipid peroxidation similar to thiobarbituric acid reactive substances. Results LPS induced-plasma TNF-α, brain TNF-α, and plasma MDA levels were significantly lower in the LPS+agomelatine group compared to the LPS+saline group (p<0.05). HVA levels and stereotype scores were significantly lower in the LPS+agomelatine group compared to the LPS+saline group (p <0.001). Conclusions Agomelatine reduced TNF-α, HVA, MDA levels, and the stereotype score in relevant models of psychosis. Our results suggest that the anti-inflammatory effect of agomelatine involved oxidant cleansing properties and that its effects on the metabolism of dopamine can play an important role in the model of psychosis.

Evaluation of Overactive Bladder in Male Antidepressant Users: A Prospective Study

Purpose In this study, we investigated overactive bladder (OAB) functions in male patients who used antidepressant drugs (ADs) that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal). Methods The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders). All the patients completed the overactive bladder-validated 8 (OAB-V8) questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Beck Depression Inventory (BDS). Results The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%), and the lowest prevalence was in patients taking sertraline (28.0%). Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. Conclusions The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors.