ABSTRACT
Objective • To explore the main mutation types and pathogenicity of the coding region of keratin 9 gene (KRT9) in Chinese Han population, and to provide reference information for the classification and prediction of clinical diagnosis of the disease with epidermolytic palmoplantar keratoderma (EPPK). Methods • 834 subjects were recruited from 278 families that were not affected by EPPK in the Chinese Han population. The mutations in the coding region of KRT9 gene were detected by using the next-generation sequencing (NGS)-based gene panel combined with Sanger sequencing. The pathogenicity analysis of variants was performed by using SIFT and Polyphen-2 prediction software. Results • A total of twelve KRT9 gene mutations were detected in the Chinese Han population based on 834 individuals from 278 families. Among the twelve different mutations, six synonymous mutations and six missense mutations were identified, respectively. The assessment of pathogenicity of KRT9 gene variants was analyzed by bioinformatics tools, such as SIFT and Polyphen-2 prediction, conservative analysis, and database query. Furthermore, these missense mutations were classified as benign or possibly benign variants. Conclusion • In this study, six missense mutations in the coding region of KRT9 gene exon were detected in the Chinese Han population. According to the American Society of Medical Genetics and Genomics (ACMG) variant classification guide, all the six variants were benign or possibly benign. However, previous reports have found that a KRT9 c.1216T>C (p.C406R) mutation was pathogenic in a pedigree with EPPK, which were inconsistent with our findings, and the pathogenicity of this mutation still has to be verified by further functional experiments.
ABSTRACT
<p><b>OBJECTIVE</b>To study the possible relationship between serum zinc levels and attention deficit hyperactivity disorder (ADHD) in Chinese children.</p><p><b>METHODS</b>Following a systematic search for case-control studies on the serum zinc levels in Chinese children with ADHD published between 2000 and 2015, a Meta analysis was conducted using Stata 12.0 software.</p><p><b>RESULTS</b>A total of 17 studies, including 2 177 children with ADHD and 2 900 normal children, were enrolled. The Meta analysis showed that serum zinc levels in children with ADHD were lower than normal children (SMD= -1.33; 95%CI: -2.22, -0.44; P=0.003). The sensitivity analysis indicated that the results were reliable. Eggerγs test did not find the existence of publication bias.</p><p><b>CONCLUSIONS</b>Serum zinc levels may be associated with susceptibility to ADHD in children.</p>
Subject(s)
Child , Humans , Attention Deficit Disorder with Hyperactivity , Blood , Case-Control Studies , Zinc , BloodABSTRACT
To elucidate the expression of epoxygenases belonging to cytochrome P-450 mono-oxygenases [CYP2] family in rat ischemic myocardium at varying reperfusion periods, and the effect of epoxygenase inhibition on the post-ischemic heart. The current study was conducted in the Department of Pharmacology, Medical College of Wuhan University, China, between September 2004 and June 2005. Rats were subjected to 40 minutes of myocardial ischemia, followed by 0, 15, 60, and 180 minutes of reperfusion. Superoxide generation was assayed by confocal microscopy, CYP2B1/2, 2C6, 2E1, 2J3 gene expressions were determined by reverse transcriptase polymerase chain reaction. Fourteen, 15-dihydroxyeicosatrienoic acid [DHET] concentration was measured by enzyme-linked immunosorbent assay. The effects of the CYP epoxygenase inhibitor N-methylsulphonyl-6-[2-propargyloxyphenyl] hexanamide [MS-PPOH] on myocardial damage and superoxide generation caused by 60 minutes of reperfusion were also evaluated. During myocardial ischemia/reperfusion, CYP2C6 and 2J3 mRNA expression were up-regulated with the peak level at 15 minutes of reperfusion; CYP2E1 gene expression decreased in a time dependent manner and reached the minimum level at 180 minutes of post-ischemia. Meanwhile, no obvious variations of CYP2B1/2 gene expression were detected during different reperfusion periods. Fourteen, 15-DHET significantly increased during reperfusion in ischemic hearts. The MS-PPOH pretreatment [15 mg/kg] effectively reduced myocardial damage and superoxide production. There are changes in gene expression of individual isozymes and an elevation of CYP epoxygenase activity involved in myocardial reperfusion injury in vivo. Epoxygenase inhibition plays a protective role in cardiac post-ischemic damage