Turker Tasliyurt

Significance of MEFV gene R202Q polymorphism in Turkish familial Mediterranean fever patients

OBJECTIVE Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. The disease is associated with mutations in the Mediterranean fever (MEFV) gene, which encodes for the pyrin protein. The aim of this study was to explore the frequency and clinical significance of the R202Q (c.605G>A) polymorphism in exon 2 of the MEFV gene in a cohort of Turkish patients with FMF. METHODS The study included 191 patients with FMF and 150 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay for the MEFV gene R202Q polymorphism. RESULTS The genotype and allele frequencies of R202Q polymorphism showed a statistically significant difference between FMF patients and controls (p<0.0001 and p=0.0004, respectively) and especially the homozygous AA genotype was significantly higher in FMF patients than healthy controls (p=0.0002; odds ratio=6.27; 95% CI=2.1-18.3). However no significant association was observed between clinical and demographic features of FMF patients and R202Qpolymorphism. CONCLUSION The results of this study showed that there was a high association between MEFV gene R202Q polymorphism and FMF. R202Q polymorphism should be included in routine molecular diagnosis of FMF patients.

Common MEFV gene mutations in Turkish patients with Behcet's disease

Behcets disease (BD) is a chronic systemic inflammatory disorder whose etiology has not been fully established yet. The MEditerranean FeVer (MEFV) gene has been identified as the cause of Familial Mediterranean Fever (FMF). BD shows similarities with FMF, in terms of clinical findings and treatments, as well as their geographical and ethnic co-occurrence. In this study we investigated common MEFV gene mutation frequencies in Turkish patients with BD in an area of Turkey where both diseases are frequently encountered. We screened 207 BD patients who had no symptoms and family history for FMF and 200 healthy subjects for five common MEFV gene mutations (E148Q, M680I, M694V, V726A, P369S) and clinical features. Seventy-five patients were found to carry a single MEFV mutation, and six patients were compound heterozygous. The difference in the frequency of the MEFV mutation between the BD and control groups was statistically significant (p<0.001, odds ratio [OR] 2.74, 95% confidence interval [CI] 1.75-4.29). The frequencies of E148Q and M680I mutations were significantly higher in the BD group (p=0.001, p=0.046, respectively). The frequency of uveitis was significantly lower in patients with the mutation than in patients without the mutation (p=0.029, OR 0.54, 95% CI 0.30-0.98). There was no statistical significance between carriers and non-carriers with respect to gender and other manifestations of BD. The frequency of the MEFV mutation was significantly higher in patients with BD compared to the healthy control group. Based on our results, MEFV mutations appear to have a role in the pathogenesis of BD.

Investigation of associations between obesity and LEP G2548A and LEPR 668A/G polymorphisms in a Turkish population.

Objective. Obesity is a complex heterogeneous disease that is caused by genes, environmental factors, and the interaction between the two. The leptin (LEP) and leptin receptor (LEPR) genes have been evaluated for polymorphisms that could potentially be related to the pathophysiology of obesity and its complications. The aim of this study was to investigate the role of LEP G2548A and LEPR 668A/G polymorphisms in the pathogenesis of obesity. Subjects. The study included 127 patients with obesity and 105 healthy controls. Polymerase chain reaction and restriction fragment length analysis for LEP G2548A and LEPR 668A/G polymorphisms were applied. Results. There was no statistically significant difference in the genotype frequencies of the LEP gene polymorphism between patients and control groups (P > 0.05). We found a difference in the LEPR genotypes between patients and controls, but this was not statistically significant (P = 0.05). Additionally, we found an increased risk of obesity in the LEP/LEPR GG/GG combined genotype (P < 0.05). Conclusion. Our findings indicate that the LEP G2548A polymorphism is not a relevant obesity marker and that the LEPR 668A/G polymorphism may be related to obesity in a Turkish population. Further researches with larger patient population are necessary to ascertain the implications of LEP and LEPR polymorphisms in obesity.

Analysis of common MDR1 (ABCB1) gene C1236T and C3435T polymorphisms in Turkish patients with familial Mediterranean fever

The multidrug resistance (MDR1) gene encodes a P-glycoprotein that plays a key role in drug bioavailability and response to drugs in different human populations. More than 50 SNPs have been described for the MDR1 gene. Familial Mediterranean fever (FMF) is considered an autosomal recessive hereditary disease, associated with a single gene named the Mediterranean fever gene (MEFV). However, about one-third of FMF patients have only one mutated allele, suggesting that this disease is expressed as an autosomal dominant trait with partial penetration or an additional gene might be responsible for the disease. We made genotype and haplotype analyses of the MDR1 gene in 142 FMF patients and 130 unrelated Turkish subjects; two MDR-1 genetic markers (C1236T and C3435T) were analyzed by PCR-RFLP analysis. FMF patients had a significantly higher frequency of the 3435 CT genotype compared with the control group (59.9% in FMF patients versus 44.6% in controls; odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.14-3.00). Based on haplotype analysis, the T-C shift was significantly more frequent in controls (14.4% versus 7.1% in FMF patients). This haplotype could be protective for FMF disease (OR = 0.45; 95%CI = 0.25-0.84). The frequency of CC-CT (1236-3435) binary genotype was significantly higher in FMF patients (14.79% versus 4.61% in controls; OR = 3.59; 95%CI = 1.40-9.20).

Prevalence of Chronic Kidney Disease in the Black Sea Region, Turkey, and Investigation of the Related Factors with Chronic Kidney Disease

We aimed to assess the prevalence of CKD in the Black Sea Region, Turkey, and to evaluate any relationship between age, gender, diabetes, obesity, hypertension, and CKD. This study was conducted in 70 different areas in Tokat Province in the Black Sea Region, in the northern part of Turkey. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine using MDRD formulas. CKD-defined estimated GFR was lower than 60 mL/min/1.73m2. A total of 1,079 persons were included in this study (mean age 41.4±17 years [range: 18–95 years], 49.4% males, 50.6% living in an urban area). Of the 1,079 individuals, 5.28% were diabetic, 22.9% were obese, and 37.8% were hypertensive. CKD was found in 62 of them (5.75%). The prevalence of CKD was 5.58% in non-diabetics and 8.77% in diabetics. No significant differences were found between two groups. The prevalence of CKD was 3.77% in non-hypertensive individuals and 8.82% in hypertensive patients, and 4.46% in non-obese and 9.31% in obese. The evident significant differences were found between groups (p < 0.0001 and p = 0.004, respectively). The prevalence of CKD increased with age within our population. A salient observation was the markedly higher prevalence of CKD in females than males (p = 0.046). There was an inverse correlation between eGFR and age (r = 0.529, p < 0.0001). The overall prevalence of CKD was 5.75% in general population. The prevalence of CKD increased with age within our population. Age, gender, obesity and hypertension were found to be significant risk factors for development of CKD in our population.

The relationship between the neutrophil-lymphocyte ratio and disease activity in patients with ulcerative colitis.

Preliminary evidence suggests that a higher neutrophil–lymphocyte ratio (NLR) may be an indicator of active ulcerative colitis (UC). However, it is not clear whether the NLR is a useful and simple indicator of clinical activity in UC after adjusting for the other inflammatory markers. We designed a retrospective study to evaluate the role of the NLR in estimating disease severity in UC patients. The study consisted of 71 patients with UC and 140 age‐ and sex‐matched healthy individuals (control group). The NLR, erythrocyte sedimentation rate, C‐reactive protein, and white blood cell count were measured. The NLR values of the active UC group were elevated compared with those of the patients with inactive UC and the controls (2.59 ± 1.47, 2.03 ± 1.07, and 1.98 ± 0.85, respectively; p = 0.005). The receiver operating characteristic revealed that the optimum NLR cut‐off point for active UC was 2.39. A multivariable logistic analysis showed that of the parameters studied, C‐reactive protein was the only parameter able to significantly discriminate active from inactive UC (B: 0.222; p = 0.017; odds ratio: 1.248; 95% confidence interval: 1.041–1.497).

Idiopathic pigmented free-floating posterior vitreous cyst

A 28-year-old female who complained of visual symptoms in the right eye was admitted to the ophthalmology clinic. She had been suffering from visual disturbance for about 5 years and her symptoms had become worse during the last 2 months. There was no previous history of trauma, infection or inflammatory disorders. A pigmented vitreous cyst was detected in her ophthalmologic examination. As the patient refused, laser cystotomy could not be performed. The pigmented vitreous cyst was possibly congenital in origin and described as a cystic choristoma from the primitive hyaloid system in the literature. The movements of the cyst, causing only transient blurring of vision, may rarely affect the visual axis. The visual acuity was 20/20 in the affected eye so it was suggested that she should be followed-up periodically for her cyst.

Insulin resistance and cardiovascular risk factors in women with PCOS who have normal glucose tolerance test

Introduction: We aimed to determine the insulin resistance in women with PCOS patients who have normal oral glucose tolerance test (OGTT) and to evaluate cardiovascular risk by measuring C-reactive protein (CRP) and carotid intimae-media thickness (CIMT). Methods: A total of 34 patients and age and body mass matched 20 healthy control subjects were included to this prospective study. Both of patients and control groups were consisted of normal oral glucose tolerance test. Insulin resistance (IR) was estimated using HOMA-IR method. CRP, lipid and hormone levels were measured. CIMT was measured by Carotid Artery B-Mode ultrasonography. Results: There was no significant difference between patients and controls in BMI, and waist circumference, lipid, TSH, LH, FSH, estradiol, and prolactin levels. Serum insulin, testosterone, DHEAS, ferritin levels and HOMA values were significantly higher in patient group. We found that 64.7% (n = 22/34) patients with PCOS had insulin resistance. Both of CIMT and CRP levels were significantly higher in the PCOS patients had BMI over 25 kg/m2. CRP levels was significantly higher in the PCOS patients had waist circumference greater than 80 cm. Conclusion: We found insulin resistance in the women with PCOS even if OGTT was normal. Our data were similar to literature, the women with PCOS have increased risk of premature atherosclerosis and metabolic syndrome.

The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.

Role of psychiatric disorders and irritable bowel syndrome in asthma patients

OBJECTIVES: The goals of the study were the following: 1) to determine the frequency of psychiatric disorders and irritable bowel syndrome in patients with asthma and 2) to compare the frequency of these disorders in patients with asthma to their frequency in healthy controls. INTRODUCTION: Patients with asthma have a higher frequency of irritable bowel syndrome and psychiatric disorders. METHODS: We evaluated 101 patients with bronchial asthma and 67 healthy subjects. All subjects completed the brief version of the Bowel Symptoms Questionnaire and a structured clinical interview for DSM-IV axis disorders (SCID-I/CV). RESULTS: There were 37 cases of irritable bowel syndrome in the group of 101 stable asthma patients (36.6%) and 12 cases in the group of 67 healthy subjects (17.9%) (p = 0.009). Irritable bowel syndrome comorbidity was not related to the severity of asthma (p = 0.15). Regardless of the presence of irritable bowel syndrome, psychiatric disorders in asthma patients (52/97; 53.6%) were more common than in the control group (22/63, 34.9%) (p = 0.02). Although psychiatric disorders were more common in asthma patients with irritable bowel syndrome (21/35, 60%) than in those without irritable bowel syndrome (31/62, 50%), the difference was not significant (p = 0.34). In asthma patients with irritable bowel syndrome and psychiatric disorders, the percentage of forced expiratory volume in 1 s (FEV1) was lower than it was in those with no comorbidities (p = 0.02). CONCLUSIONS: Both irritable bowel syndrome and psychiatric disorders were more common in asthma patients than in healthy controls. Psychiatric disorders were more common in asthma patients with irritable bowel syndrome than in those without irritable bowel syndrome, although the differences failed to reach statistical significance. In asthma patients with IBS and psychiatric disorders, FEV1s were significantly lower than in other asthma patients. It is important for clinicians to accurately recognize that these comorbid conditions are associated with additive functional impairment.