The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients

OBJECTIVE: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). METHODS: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel (1)H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. RESULTS: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). CONCLUSION: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings

Association of SNAP-25 gene Ddel and Mnll Polymorphisms with adult attention deficit hyperactivity disorder

Objective The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters. Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25 polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the Turkish population. Methods: Our study comprised unrelated 139 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. Results: SNAP-25 DdelI polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher scores in the 1st and 3rd parts of adult ADD/ADHD Scale. Conclusion: We detected a significant association of the MnlI polymorphism in our ADHD sample which was similar to previous findings. Our study also revealed that SNAP-25 MnlI polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population. © 2014 Korean Neuropsychiatric Association

Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants

Q1Q1Artículo original445-453Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) >0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness

Role of 2.4 GHz radiofrequency radiation emitted from Wi-Fi on some miRNA and faty acids composition in brain

The purpose of this study is to investigate the effects of 2.4 GHz Wi-Fi exposure, which is continuously used in the internet connection by mobile phones, computers and other wireless equipment, on microRNA and membrane and depot fatty acid composition of brain cells. Sixteen Wistar Albino rats were divided equally into two groups such as sham and exposure. The rats in the experimental group (n = 8) were exposed to 2.4 GHz RFR emitted from a Wi-Fi generator for 24 h/day for one year. The animals in the control group (n = 8) were kept under the same conditions as the experimental group, but the Wi-Fi generator was turned off. At the end of the study, rats were sacrificed and brains were removed to analyze miRNA expression and membrane and depot fatty acids of brain cells. We analyzed the situation of ten different miRNA expressions and nineteen fatty acid patterns in this study. We observed that long-term and excessive exposure of 2.4 GHz Wi-Fi radiation increased rno-miR-181a-5p, phosphatidylserine (PS) and triacylglycerol (TAG) in the brain. In conclusion, 2.4 GHz Wi-Fi exposure has the potential to alter rno-miR-181a-5p expression and the fatty acid percentage of some membrane lipids such as phospholipid (PL), phosphatidylserine (PS) and triacylglycerol (TAG), which are depot fats in the brain. However, the uncontrolled use of RFRs, whose use and diversity have reached incredible levels with each passing day and which are increasing in the future, may be paving the way for many diseases that we cannot connect with today

SNP Variation in MicroRNA Biogenesis Pathway Genes as a New Innovation Strategy for Alzheimer Disease Diagnostics: A Study of 10 Candidate Genes in an Understudied Population From the Eastern Mediterranean

Erdal, Mehmet Emin/0000-0002-6191-2930;WOS: 000383914600002PubMed: 26796812Alzheimer disease (AD) is a common complex neurodegenerative disorder accounting for nearly 50% to 70% of dementias worldwide. Yet the current diagnostic options for AD are limited. New diagnostic innovation strategies focusing on novel molecules and pathways are sorely needed. In this connection, microRNAs (miRNAs) are conserved small noncoding RNAs that regulate posttranscriptional gene expression and are vital for neuronal development and its functional sustainability. Conceivably, biological pathways responsible for the biogenesis of miRNAs represent a veritable set of upstream candidate genes that can be potentially associated with the AD pathophysiology. Notably, whereas functional single-nucleotide polymorphisms (SNPs) in miRNA biogenesis pathway genes have been studied in other complex diseases, surprisingly, virtually no such study has been conducted on their relevance in AD. Moreover, novel diagnostics identified in easily accessible peripheral tissues such as the whole blood samples represent the initial entry or gateway points on the biomarker discovery critical path for AD. To the best of our knowledge, we report here the first association study of functional SNPs, as measured by real-time PCR in 10 upstream candidate genes critically situated on the miRNA biogenesis pathway, in a large sample of AD patients (N=172) and healthy controls (N=109) in a hitherto understudied world population from the Mersin region of the Eastern Mediterranean. We observed a significant association between 2 candidate genes and AD, TARBP2 rs784567 genotype and AD ((2)=6.292, P=0.043), and a trend for RNASEN rs10719 genotype ((2)=4.528, P=0.104) and allele (P=0.035). Functional SNP variations in the other 8 candidate genes (DGCR8, XPO5, RAN, DICER1, AGO1, AGO2, GEMIN3, and GEMIN4) did not associate with AD in our sample. Given the putative biological importance of miRNA biogenesis pathways, these emerging data can provide a new foundation to stimulate future debate and genetic investigations of AD, focusing on new molecular mechanisms such as miRNA biogenesis, particularly in accessible peripheral tissues for novel molecular diagnostics for dementia.University of Mersin [BAP-SBE TB]Supported by an intramural research grant from the University of Mersin [BAP-SBE TB (S.G.Y.) 2010-4]

Can Peripheral MicroRNA Expression Data Serve as Epigenomic (Upstream) Biomarkers of Alzheimer's Disease?

Erdal, Mehmet Emin/0000-0002-6191-2930;WOS: 000381214300002PubMed: 27501295Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. However, biomarkers that require testing in the brain tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs (miRNAs) are responsible for control of gene expression at the posttranscriptional level and are essential for the function of neuronal networks and neuronal survival. miRNA expression can impact the regulation of APP (amyloid beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1 (beta-secretase 1) genes in the brain that were previously implicated in AD pathophysiology. Little is known, however, on the extent to which peripheral tissue (e.g., whole blood) miRNA variation might offer clinical predictive value for AD. Moreover, few studies have examined multiple peripheral miRNA expression data at the same time. We report here, to the best of our knowledge, the first whole-blood-based and parallel study of seven miRNAs (hsa-miR-9-5p, hsa-miR-29a-3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR-125b5p) in relation to AD susceptibility. Notably, these miRNAs are situated "upstream" to the genes implicated in AD. We measured the whole-blood miRNA expression by a real-time polymerase chain reaction in a large study sample (n = 281), comprising patients with AD (n = 172) and healthy controls (n = 109). A reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR-106b-5p, and hsa-miR-107 was significantly associated with an increased risk of AD (p 0.05). In conclusion, these observations warrant replication in larger samples while making a contribution to translational research, precision medicine, and biomarker literatures, by expanding the current efforts for AD diagnostic innovation to the realm of epigenomic pathways such as miRNA expression variation among patients.Mersin University (BAP-SBE TB) [2010-4]This study was supported by the intramural research fund of the Mersin University (BAP-SBE TB [S.G.Y.] 2010-4). This article is based on the work done in the first author's PhD thesis (S.G.Y.); it has never been published as a journal article, and it represents original data and research. The authors thank the research participants who volunteered their time for this study

Onsekiz haftalık gebede plasenta akretaya bağlı uterin rüptür: Olgu sunumu

Amaç: Plasenta akretaya bağlı uterin rüptür gözlenen 18 haftalık gebeliğe sahip nadir görülen bir olgunun sunulması Çatışmanın Yapıldığı Yer: Pamukkale Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı Materyal ve Metod: 18. gebelik kaftanımla polikliniğimize başvuran , hemoperitoneum ve uterus dışında ölü fetus tesbit edilen bir gebe Bulgular: Laparotomide uterin rüptür tesbit edilerek subtotal histerektomi yapıldı. Yapılan patolojik inceleme sonucunda plasenta akretaya bağlı uterin rüptür teshil edildi. Sonuç: Erken gebelik döneminde, a: görülsede, plasenta akretanın spontan uterin rüptür sebebi olabileceği düşünülmelidir