Keloid Scarring: Understanding the Genetic Basis, Advances, and Prospects

Keloid disease is a fibroproliferative dermal tumor with an unknown etiology that occurs after a skin injury in genetically susceptible individuals. Increased familial aggregation, a higher prevalence in certain races, parallelism in identical twins, and alteration in gene expression all favor a remarkable genetic contribution to keloid pathology. It seems that the environment triggers the disease in genetically susceptible individuals. Several genes have been implicated in the etiology of keloid disease, but no single gene mutation has thus far been found to be responsible. Therefore, a combination of methods such as association, gene-gene interaction, epigenetics, linkage, gene expression, and protein analysis should be applied to determine keloid etiology

Association of rs1800624 Polymorphism in Receptor for Advanced Glycation End Products Gene Promoter with the Risk of Diabetic Nephropathy

Background and Aim: Although the molecular mechanisms involved in the pathogenesis of diabetic nephropathy are still unclear, the role of advanced glycation end products (AGEs) and their associated receptors (AGER) in initiating the inflammatory process in this disease has attracted attention. The aim of this study was to investigate the relationship between rs1800624 polymorphism of AGER gene with risk of diabetic nephropathy in Iranian population. Materials and Methods: In this case-control study, patients were divided into two groups, group1 without diabetic nephropathy (n = 71) and group2 with diabetic nephropathy (n = 79). TETRA-Primer ARMS-PCR technique was used to determine the frequency of genotype and allele of rs1800624 polymorphism in the promoter region of AGER gene. Using standard methods, biochemical tests including measurement of glucose, creatinine, glycosylated hemoglobin and blood urea nitrogen and calculation of eGFR were performed. We used SPSS and FAMHAP softwares for data analysis. Results: The results showed that AA genotype rs1800624 polymorphism in the promoter region of the AGER gene may be associated with an increased risk of diabetic nephropathy. Allele analysis also showed that allele A of the polymorphism may be associated with an increased risk of developing nephropathy, although the results were not statistically significant between the two groups in relation to rs1800624 polymorphism. Conclusion: The findings of this study showed that there was no statistically significant relationship between rs1800624 polymorphism in AGER gene with diabetic nephropathy in the Iranian population, but increase in sample size may result in a tendency to develop diabetic nephropathy

De novo Ring Chromosome 6 in a Child with Multiple Congenital Anomalies

Ring chromosome 6, especially if it is de novo, is a rare occurrence. The phenotype of patients with ring chromosome 6 can be highly variable ranging from almost normal to severe malformations and mental retardation. The size and structure of the ring chromosome as well as the level of mosaicism are important factors in determining the clinical phenotype. Here we report an eight month-old child, a product of a non consanguineous marriage, who presented with developmental retardation, hypertelorism, microcephaly, flat occiput, broad nasal bridge, large ears, micrognathia, wide spaced nipples, protruding umbilicus, short stubby fingers, clinodactyly, single palmar crease, short neck with no obvious webbing, and congenital heart defect. Conventional karyotyping and Whole Chromosome Paint of the peripheral leukocytes showed 46,XY,r(6)(p25q27) karyotype with plausible breakpoints at p25 and q27 end. Conventional karyotyping of both parents showed normal karyotype. To the best of our knowledge, this is the first report of a Malay individual with ring chromosome 6, and this report adds to the collective knowledge of this rare chromosome abnormality

Haplotype Analysis of RAGE Gene Polymorphisms and Association with Increased Risk of Diabetic Nephropathy

Background: The present study aimed at evaluating the association between the -429T/C and - 374T/A polymorphisms of RAGE (Receptor for Advanced Glycation End Products) gene promoter and diabetic nephropathy as well as examining its possible application as candidate markers of diabetic nephropathy among the population of Qazvin, Iran. Methods: In this study, the diabetic patients were divided into the two groups of with or without nephropathy. The frequency of genotype and allele were determined using TETRA-Primer ARMSPCR. Hardy-Weinberg equilibrium test and correlation of polymorphisms, odds ratio (OR), and FAMHAP software were used for haplotype analysis. Results: Based on our data, the CC genotype of -429T/C polymorphism may play a protective role against the development of nephropathy (OR=0.586, 95%; CI: 0.158-2.167) while, the AA genotype may be associated with increased risk of the disease (OR=1.889, 95%; CI: 0.454-7.854). Allele’s analysis revealed that the C allele of -429T/C polymorphism maybe protective against the appearance of nephropathy (OR=0.794, 95%; CI: 0.48-1.314) whereas, the A allele may be related to increased risk for nephropathy (OR=1.452, 95%; CI: 0.783-2.695). Haplotype analysis demonstrated that there was no significant correlation between the two -429T/C and -374T/A SNPs (χ2=5.125, p value=0.135). However, it was found that the CA haplotype may have a protective effect against the development of nephropathy (OR=0.48, 95%; CI: 0.14-1.64) while, the TA haplotype may increase the risk of the disease (OR=2.06, 95%; CI:1.01-4.23). Conclusion: Overall, no correlation between the -374T/A and -429T/C polymorphisms and the haplotypes in RAGE gene and the occurrence of diabetic nephropathy, was established. Keywords: Nephropathy, Type 2 Diabetes, Haplotype, Receptor for Advanced Glycation End Products, SNP, Iran Citation: Tavakoli A, Salahshourifar I, Hajialilo

Overexpression of MMP13

Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P=0.011) and tumor staging (P=0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P<0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC

The first Malay database toward the ethnic-specific target molecular variation

BACKGROUND:The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS:Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS:This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background

Investigation of Long Non-coding RNA HOX A11-AS Expression in Iranian Patients with Glioblastoma: A Quantitative Study

Background and Objectives: Glioblastoma is one of the most malignant and common brain tumors, accounting for about half of all gliomas. Glioblastoma is a central nervous system tumor that originates from the glial tissue of the brain. The present study aimed to investigate changes in the expression of long non-coding RNA HOXA11-AS as a possible biomarker in glioma.   Methods: For the purposes of the present study, first, the medical records of the patients in Imam Hossein Hospital in Tehran, Iran were reviewed. The ethical considerations were respected as well; accordingly, written informed consent was obtained from the patients and the code of ethics was achieved as well. Finally, the paraffin blocks, including the biopsy of brain tumor tissue of the patients who referred to Imam Hossein Hospital during 2015-17 were collected and their degrees were confirmed by the pathologist. In total, 50 samples of grades 1 and 2 as well as 50 samples of grades 3 and 4 were examined in this research project. The RNA extraction and cDNA synthesis were performed for all the tissue samples donated by the patients. Subsequently, a specific primer and probe were designed and the expression of the HOXA11-AS gene was investigated using real-time polymerase chain reaction technique. The mean age of the subjects was 43.70±16.416 years. The collected data were analyzed in SPSS software (version 20) using descriptive and analytical statistics. Moreover, the expression levels of this gene in lower- and higher-grade tumor tissues were compared using the unpaired samples t-test.   Results: Based on the results, the tumor samples with grade three and four underwent a 2.76 fold increase in expression (fold change), compared to tumor samples with grade one and two. This difference was statistically significant.   Conclusion: Based on the findings, it can be concluded that the expression of the HOXA11-AS gene has a significant positive relationship with the degree of disease (P=0.0002)

Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure. Up to 50% of all DCM cases have a genetic background, with variants in over 250 genes reported in association with DCM. Whole-exome sequencing (WES) is a powerful tool to identify variants underlying genetic cardiomyopathies. Via WES, we sought to identify DCM causes in a family with 2 affected patients. Methods WES was performed on the affected members of an Iranian family to identify the genetic etiology of DCM. The candidate variant was segregated via polymerase chain reaction and Sanger sequencing. Computational modeling and protein-protein docking were performed to survey the impact of the variant on the structure and function of the protein. Results A novel single-nucleotide substitution (G > A) in exon 9 of MED12, c.1249G > A: p.Val417Ile, NM_005120.3, was identified. The c.1249G > A variant was validated in the family. Bioinformatic analysis and computational modeling confirmed that c.1249G > A was the pathogenic variant responsible for the DCM phenotype. Conclusion We detected a novel DCM-causing variant in MED12 using WES. The variant in MED12 may decrease binding to cyclin-dependent kinase 8 (CDK8), affect its activation, and cause alterations in calcium-handling gene expression in the heart, leading to DCM

Evaluation of LncRNA uc.173 and Occludin in Iranian Patients with Inflammatory Bowel Disease Compared with Healthy Individuals

Background & Objective: Inflammatory bowel disease (IBD) is characterized by the chronic gastrointestinal inflammation. The two common forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD) that are distinguished by their location and depth of involvement in the diffuse inflammation of the colonic mucosa and affects the rectum (proctitis). A novel class of LncRNAs transcribed from ultra-conserved regions (UCRs) is a recently identified ultra-conserved region (T-UCR) transcript that is involved in the cellular function in a variety of pathways. However, the regulation of LncRNA uc.173 in IBD remains to be fully elucidated. In this study, we aimed to examine the expression of LncRNA uc.173 and Occludin genes in an Iranian population with inflammatory bowel disease. Materials & Methods: This case-control study was performed on 33 inflammatory bowel disease patients including 13 Crohn's disease, 20 ulcerative colitis and 20 healthy controls. The mRNA levels of LncRNA uc.173 and Occludin genes were assessed using the quantitative Real-time polymerase chain reaction. The B2M was used as an internal control. The 2 -ΔΔCq method was used to determine the expression fold changes. Results: Statistically, the level of the LncRNA uc.173 gene expression between the UC and normal tissues increased significantly(P=0.0024). Also, the expression analysis revealed no significant difference between the samples of CD patients compared to the controls (P>0.05). In order to further evaluate the role of LncRNA uc.173 in IBD, the associations between the transcript levels of the LncRNA uc.173 and Occludin mRNA demonstrated significant difference in the CD tissue (R=0.59; P=0.002). In our study, the mRNA expression of Occludin gene did not show any changes in the IBD patients compared to the healthy controls. Conclusion: The increased expression of LncRNA uc.173 in the tissues of UC patients may be considered as a diagnostic or prognostic biomarker. Also, there was no correlation found between Occludin and LncRNA uc.173 expressions in the IBD patients' tissues