Seniz Demiryürek

Association Between the T-593A and C6982T Polymorphisms of the Osteopontin Gene and Risk of Developing Nephrolithiasis

BACKGROUND AND AIMS Increased synthesis of several urinary proteins including osteopontin (OPN) has been shown to be associated with stone formation within the urinary tract. The objective of this study was to analyze the genotype distributions and allele frequencies for OPN gene promoter T-593A and C6982T (in exon 7) polymorphisms among patients with kidney stones. METHODS In this case-control study, the study group consisted of 121 patients with radiologically confirmed nephrolithiasis. Genomic DNA from patients and control cases (n = 100) was analyzed by single-strand conformation polymorphism method and nucleotide sequence analysis. RESULTS Homozygous carriers of the T-593T genotype were more frequent, but carriers of the A-593A genotype were less frequent in patients than in controls. There was also an increase in -593T allele (88% in patients vs. 79% in controls) and decrease in -593A allele frequencies (21% in control vs. 12% in patients) in the nephrolithiasis groups (p = 0.013). The carriers of C6982C genotype were less frequent, but marked increases in T6982T genotype (25.6% in patients vs. 7% in controls, p = 0.001) and 6982T allele frequency (53.3% in patients vs. 37.5% in controls, p = 0.001) were noted in patients of Turkish ancestry. CONCLUSIONS These results are the first to demonstrate the existence of T-593A promoter polymorphism of the OPN gene and significant association with risk of developing nephrolithiasis. Our results showed marked associations between polymorphisms (C6982T and T-593A) of the OPN gene and the stone-forming phenotypes in the Turkish population.

Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin-II (UTS2) Gene, Diabetes Mellitus, and Diabetic Retinopathy

Purpose: To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish population. Methods: Total number of 280 patients with DR (nonproliferative DR 170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic controls (without DR) were included to this study. The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1 program was used for molecular modeling analysis. Results: Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele frequency (52.7% in diabetic control vs. 76.4% in PDR, P < 0.0001) frequency in PDR group were detected. However, there were no changes in genotype and allele frequencies for T21M in NPDR group. There were decreases in the S89N genotype (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were associated with NPDR patients (P < 0.001), but only MN (P < 0.001) and TS haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis showed that these two polymorphisms changed the 3D structure of UTS2, and provided interactions with neighboring residues. Conclusion: The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.

Protective effects of Y-27632 on acute dichlorvos poisoning in rats.

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.

Protective activity of ischemic preconditioning on rat testicular ischemia: Effects of Y-27632 and 5-hydroxydecanoic acid

BACKGROUND/PURPOSE The aim of this study was to investigate the role of ischemic preconditioning (IPC) on ischemia/reperfusion (I/R)-induced injury of rat testis and determine the effects of 5-hydroxydecanoic acid (5-HD), a selective K(ATP) channel antagonist, and Y-27632, a selective Rho kinase inhibitor, on IPC. METHODS I/R injury was induced by 180 min ischemia and 60 min reperfusion of testis. There were 5 groups. Group 1 served as untreated controls. The rats in Group 2 were subjected to I/R only. In Group 3, 3 cycles of IPC (5 min transient ischemia plus 5 min reperfusion) were performed prior to I/R. In groups 4 and 5, the rats were treated as in Group 3 but received intraperitoneal injections of 0.3 mg/kg Y-27632 or 10 mg/kg 5-HD prior to IPC, respectively. RESULTS I/R led to severe histopathological lesions in the rat testis and significantly lowered the scoring. I/R resulted in significant elevation in tissue lipid peroxide levels, myeloperoxidase (MPO) activity, and total antioxidative capacity (TAC), total oxidative status, and oxidative stress index levels. Protective effects of IPC on I/R-induced testicular injury of rats were observed with the significant recovery in these biochemical parameters. Y-27632 treatment led to a significant decrease in MPO activity, but there were no significant changes in the remaining parameters. Effects of IPC were blocked by 5-HD except in the TAC levels. CONCLUSION Our results showed that IPC protected rat testis against I/R-induced injury via activation of KATP channels. Additionally, Rho kinase inhibition preserved the effects of IPC in testis.

Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls. mRNA was extracted from blood samples, and real-time polymerase chain reaction was performed for gene expressions by using a dynamic array system. Low levels of TRP channel expressions in the controls were markedly potentiated in NVAF group. We observed marked increases in MCOLN1 (TRPML1), MCOLN2 (TRPML2), MCOLN3 (TRPML3), TRPA1, TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPV3, TRPV4, TRPV5, TRPV6, and PKD2 (TRPP2) gene expressions in NVAF patients (P < 0.05). However, there was no change in PKD1 (TRPP1) gene expression. This is the first study to provide evidence that elevated gene expressions of TRP channels are associated with the pathogenesis of NVAF.

Maternal Iron Deficiency Anemia as a Risk Factor for the Development of Retinopathy of Prematurity.

BACKGROUND Retinopathy of prematurity is a proliferative vascular disease affecting premature newborns and occurs during vessel development and maturation. The aim of this study was to evaluate the maternal iron deficiency anemia as possible risk factors associated with the development of retinopathy of prematurity among premature or very low birth weight infants. METHODS In this study, mothers of 254 infants with retinopathy of prematurity were analyzed retrospectively, and their laboratory results of medical records during pregnancy were reviewed for possible iron deficiency anemia. RESULTS In a cohort of 254 mothers of premature infants with retinopathy of prematurity, 187 (73.6%) had iron deficiency, while the remaining 67 (26.4%) mothers had no deficiency. Babies born to mothers with iron deficiency anemia with markedly decreased hemoglobin, hematocrit, mean corpuscular volume, serum iron, and ferritin levels were more likely to develop retinopathy of prematurity. CONCLUSIONS Our results are the first to suggest that maternal iron deficiency is a risk factor for the development of retinopathy of prematurity. Our data suggest that maternal iron supplementation therapy during pregnancy might lower the risk of retinopathy of prematurity.

The Clinical Implications of Todd Paralysis in Children With Benign Rolandic Epilepsy

The aim of this study was to describe the clinical and electroencephalographic (EEG) findings of postictal Todd paralysis in benign rolandic epilepsy of childhood and find out the possible correlation with migraine. Based on International Headache Society pediatric migraine criteria, patients were investigated for migraine, and 12 of the 108 patients with benign rolandic epilepsy (6 girls and 6 boys, 11.1%) were found to have postictal Todd paralysis. Ten of these 12 patients (83.3%) had pediatric migraine based on the diagnostic criteria. We showed comorbidity of migraine and benign rolandic epilepsy with postictal Todd paralysis in children. Increased incidence of migraine in the present study suggest that children who have benign rolandic epilepsy and postictal Todd paralysis are more likely to have migraines.

CYP gene expressions in obesity-associated metabolic syndrome

PURPOSE The contribution of cytochrome P450 (CYP) gene expressions in metabolic syndrome (MetS) has not been elucidated, and was the aim of this study. METHODS A total of 51 MetS patients and 41 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a dynamic array system. RESULTS We observed marked suppressions in CYP2A6 (p=0.0123), CYP4F2 (p=0.0005), CYP3A5 (p=0.0003), and CYP17A1 (p<0.0001) gene expressions in MetS patients. CONCLUSIONS This is the first study to provide evidence that depressed expressions of CYP2A6, CYP4F2, CYP3A5, and CYP17A1 genes may play a role in MetS.

Evidence for elevated ( LIMK2 and CFL1 ) and suppressed ( ICAM1 , EZR , MAP2K2 , and NOS3 ) gene expressions in metabolic syndrome

The metabolic syndrome (MetS) is a common multicomponent condition including abdominal obesity, dyslipidemia, hypertension, and hyperglycaemia. The aim of this study was to investigate the associations of the expression of a panel of signalling genes with the MetS in a Turkish population. A total of 54 MetS patients and 42 healthy controls with similar age and sex were included to this study. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for gene expressions using a BioMark 96.96 dynamic array system. We observed marked increases in LIM kinase 2 (LIMK2) and cofilin 1 (CFL1) gene expressions in MetS patients. However, there were significant decreases in intercellular adhesion molecules 1 (ICAM1), ezrin (EZR), mitogen-activated protein kinase kinase 2 (MAP2K2), and nitric oxide synthase 3 (NOS3) gene expressions in MetS patients. Additionally, no marked changes were noted in other 15 genes studied. This is the first study to provide evidence that activation of LIMK2/CFL1 pathway may play an important role in MetS.

Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine

BACKGROUND Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. AIM This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. MATERIALS AND METHODS A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. RESULTS Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. CONCLUSION This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.