A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites.

The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

Assessing the Sensitivity of Nested PCR Followed by Direct Sequencing on Exosomal DNA for EGFR Mutation Detection in NSCL

Background: Early and minimally invasive detection of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients is a promising tool to select patients for targeted therapy in order to improve their prognosis. This study aimed to identify a sensitive, cost-effective, and easily accessible noninvasive method for detecting the EGFR-targetable mutations in the plasma exosomal DNA (exoDNA)+ of patients with NSCLC. Methods: This retrospective observational study was conducted over 10 months, from December 2022 to October 2023, at Masih Daneshvari Hospital in Tehran, Iran. A total of 30 patients with stage II-IV NSCLC and targetable mutation in the EGFR gene were included in the study. Nested PCR and Sanger sequencing were used to evaluate EGFR mutations in the DNA extracted from circulating exosomes. Results: The study found a sensitivity of 76.6% for EGFR mutation detection on exoDNA compared to tissue results. No significant impact was observed based on tumor staging, histology, mutation type, smoking status, gender, or age. Conclusion: Therapeutically targetable driver mutations in the EGFR gene can be accurately detected using nested PCR followed by direct sequencing of plasma exoDNA from patients with NSCLC. This approach facilitates timely and more personalized treatment for NSCLC patients, ultimately improving patient prognosis. Additionally, this method reduces the reliance on invasive tissue biopsies and their associated complications.

An A10398G mitochondrial DNA alteration is related to increased risk of breast cancer, and associates with Her2 positive receptor.

Breast cancer is the most common malignancy and the second leading cause of cancer deaths among women worldwide after lung cancer. Mitochondria play a central role in the regulation of cellular function, metabolism, and cell death in cancer cells. We aim to examine the mitochondrial polymorphisms of complex I in association with breast cancer in an Iranian cohort.This experimental study includes 53 patients with breast cancer and 35 healthy control patients. In addition, tumor-adjacent normal breast tissue was obtained from each patient. The DNA of the tissue cells was extracted and analyzed for complex I mutations using a PCR sequencing method. Our results show 94 mtDNA complex I variants in tumor tissues. A10398G was the most prevalent polymorphism and strongly correlated with Her2 receptor in tumor tissue samples. Mitochondrial DNA (mtDNA) mutations have been widely linked to the etiology of numerous disorders. The mtDNA mutations screening on A10398G along with other mutations might provide insight on the role of mitochondrial mutations in breast cancer.

Genetic Variants of Cytochrome b-245, Alpha Polypeptide Gene and Premature Acute Myocardial Infarction Risk in an Iranian Population.

BACKGROUND: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. METHODS: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011). CONCLUSIONS: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.

In silico finding of Putative Cis-Acting Elements for the Tethering of Polycomb Repressive Complex2 in Human Genome.

Polycomb Repressive Complex2 maintains a predetermined state of transcription which constitutes a cellular memory stable over many cell divisions. Since this complex acts through the regulation of chromatin structure, it is important to understand how it is recruited to chromatin. The specific target sequences of this complex such as PRE (polycomb repressive element) have not been completely recognized in human genome. In this study, we have compared the target sequences of this complex with non-target genes in tumor cell lines. Through in silico and statistical analyses, we have identified some motifs which are over-represented in target genes against non-target genes. Analyzing these motifs shows some transcription factors which are potential recruiters of Polycomb repressive complex2.