Related Genes In Patients Research Articles

High frequency of rare copy number variants affecting functionally related genes in patients with structural brain malformations

During the past years, significant advances have been made in our understanding of the development of the human brain, and much of this knowledge comes from genetic studies of disorders associated with abnormal brain development. We employed array-comparative genomic hybridization (CGH) to investigate copy number variants (CNVs) in a cohort of 169 patients with various structural brain malformations including lissencephaly, polymicrogyria, focal cortical dysplasia, and corpus callosum agenesis. The majority of the patients had intellectual disabilities (ID) and suffered from symptomatic epilepsy. We detected at least one rare CNV in 38 patients (22.5%). All genes located within the rare CNVs were subjected to enrichment analysis for specific Gene Ontology Terms or Kyoto Encyclopedia of Genes and Genomes pathways and to protein-protein network analysis. Based on these analyses, we propose that genes involved in "axonal transport," "cation transmembrane transporter activity," and the "c-Jun N-terminal kinase (JNK) cascade" play a significant role in the etiology of brain malformations. This is to the best of our knowledge the first systematic study of CNVs in patients with structural brain malformations and our data show that CNVs play an important role in the etiology of these malformations, either as direct causes or as genetic risk factors.

Measuring mRNA level expression of tumor necrosis factor α and its receptors related genes in patients with systemic sclerosis

Measuring mRNA level expression of tumor necrosis factor α and its receptors related genes in patients with systemic sclerosis

Increased vascular permeability after cardiopulmonary bypass in patients with diabetes is associated with increased expression of vascular endothelial growth factor and hepatocyte growth factor

Several inflammatory mediators such as vascular endothelial growth factor and hepatocyte growth factor are known to play a critical role in the regulation of vascular permeability and angiogenesis. We studied the serum levels of growth factors and gene expression profiles of genes involved in growth factor signaling in the peripheral blood of patients with and patients without diabetes following cardiopulmonary bypass and cardioplegic arrest. Serum and total RNA were obtained from the blood samples collected from patients with diabetes and matched patients without diabetes (n = 7 patients each) who had coronary artery bypass graft before and 6 hours and 4 days after cardiopulmonary bypass/cardioplegic arrest. The cytokine panel, consisting of growth factors such as vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor, and epidermal growth factor, was quantified in patients with diabetes and patients without diabetes before and 6 hours and 4 days post-cardiopulmonary bypass/cardioplegic arrest using multiplex cytokine quantification system. cDNA microarray analysis was performed and fold-change was calculated. Length of hospitalization (10 vs 6 days; P = .04) and weight gain (5 vs 2.5 kg; P = .001) were significantly greater for patients with diabetes compared with patients without diabetes. The serum levels of vascular endothelial growth factor and hepatocyte growth factor were significantly elevated in patients with diabetes when compared with patients without diabetes before versus 6 hours post-cardiopulmonary bypass/cardioplegic arrest. In addition, significantly elevated mRNA expression of hypoxia-inducible factor-1alpha, cyclic adenosine monophosphate response element binding protein, and E1A binding protein p300 (more than twofold) was observed 4 days post-cardiopulmonary bypass/cardioplegic arrest exclusively in patients with diabetes. The differential profile of gene and protein expression of growth factors and their related genes in patients with diabetes and patients without diabetes could be associated with increased edema and weight gain in patients with diabetes after cardiopulmonary bypass/cardioplegic arrest.

Relationship between platelet activation related factors and polymorphism of related genes in patients with coronary heart disease of blood-stasis syndrome

To comparatively study the expressive conditions of platelet activation related factors (GP I b, GP II b- III a and GMP-140) in healthy subjects and patients with coronary heart disease (CHD) of blood-stasis (BS) or non-blood-stasis (non-BS) syndrome, and to analyze the relationship between the activities of various glycoproteins and the polymorphism of genes. With case control design adopted, patients with the CHD (40 of BS, 37 of non-BS) and 39 healthy subjects for control, all fitting to the inclusion criteria, were selected in this study. The number of affected coronary branches was recorded by the contrast examination. The mean fluorescence intensity (MFI) of GP I b, GP II b- III a, and GMP-140 (CD42b, CD61, CD62p) in patients and healthy persons was measured with flow cytometry, the polymorphism of HPA-3 gene was detected by Taqman probe technique and that of HPA-2 gene was determined by gene sequencing. MFI of CD61 and CD62p was higher in the CHD patients than in the healthy control, which was also higher in patients of BS syndrome than in patients of non-BS syndrome (P<0.05); MFI of CD42b was lower in the CHD patients than in the healthy control (P<0.05), but showing insignificant difference between BS and non-BS syndrome (P>0.05); at the same time, no significant difference of all the above-mentioned three MFI could be found in patients with various numbers of affected coronary branches, neither in patients with different genotypes at GP II b HPA-3 and GP I b HPA-2 polymorphism loci (P>0.05). (1) The activities of GP II b- III a and GMP-140 were obviously increased in the genesis and developing process of CHD and CHD of BS syndrome, and so they could be taken as one of the objective indexes for microscopic diagnosis of BS syndrome. (2) The level of GP I b was lower in CHD patients than in healthy persons, but it was not a sensitive indicator for BS syndrome of CHD. (3) Levels of GP II b- III a, GP I b and GMP-140 were not related with the number of affected coronary branches in CHD patients. (4) The changes in amino-acids expression induced by the two loci brought no significant influence on GP I b and GP II b- III a activities.