Sjogren's syndrome: Everything you always wanted to know about genetic and epigenetic factors.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by a wide spectrum of glandular and extra-glandular features. Genetic and epigenetic factors play an important role in the disease susceptibility and phenotype. There are a multitude of genes that have been identified as implicated in the pathogenesis of pSS, both in HLA and extra-HLA regions with a strong contribution given by genes in interferon signalling pathways.

Large-scale DNA sequencing identifies rare variants associated with Systemic Lupus Erythematosus susceptibility in known risk genes.

The identification of rare genetic variants associated to Systemic Lupus Erythematosus (SLE) could also help to understand the pathogenic mechanisms at the basis of the disease. In this study we have analyzed a cohort of 200 Italian SLE patients in order to explore the rare protein-coding variants in five genes (TNFAIP3, STAT4, IL10, TRAF3IP2, and HCP5) already investigated for commons variants found associated in our previous studies. Genomic DNA of 200 SLE patients was sequenced by whole exome sequencing.

Low expression levels of miRNA-155 and miRNA-499a are associated with obesity in Type 2 diabetes.

This study investigated a possible correlation between three circulating miRNAs, previously observed to be associated to diabetic polyneuropathy, and the obesity condition. The expression levels of miR-128a, miR-155 and miR499a were evaluated in 49 participants with Type 2 diabetes, divided into different groups based on the presence or absence of obesity and central obesity. The analyses revealed a significant decrease of miR-155 and miR-499a expression levels in obese subjects.

ATG5 gene expression analysis supports the involvement of autophagy in microangiopathic complications of type 2 diabetes.

Background And Aims: Type 2 diabetes (T2D) hyperglycaemia alters basal autophagy. Since autophagy is an essential cellular process, our aim was to investigate the ATG5 (autophagy-related 5) gene expression level and genetic variants in a cohort of diabetic patients, characterized for the presence of microangiopathic complications.

Methods And Results: the expression levels of ATG5 were evaluated in PBMCs from 48 T2D patients with an extensive evaluation for microangiopathic complications.

Overexpression in Sjögren's Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with Gene Expression.

Background: The gene encodes for the protease enzyme Furin, which promotes proteolytic maturation of important regulators of the immune response, and also enhances the secretion of interferon-γ (IFN). Several studies have suggested its possible involvement in the pathogenesis of chronic inflammatory diseases.

Methods: We investigated the gene expression level in peripheral blood mononuclear cells isolated from Sjögren's Syndrome (SS) patients and healthy controls and we evaluated a possible correlation with gene expression.

Role of the Vitamin D Receptor (VDR) in the Pathogenesis of Osteoporosis: A Genetic, Epigenetic and Molecular Pilot Study.

The vitamin D receptor (VDR) regulates bone development and calcium homeostasis, suggesting a central role in musculoskeletal diseases such as osteoporosis (OP). Several studies have examined the contribution of polymorphisms and epigenetic signatures in bone metabolism and OP risk, with sometimes inconclusive results. Our study aimed to explore the association between genetic variability, expression and the methylation pattern of with the risk of OP in a cohort of Caucasian patients.

Alteration of Mitochondrial DNA Copy Number and Increased Expression Levels of Mitochondrial Dynamics-Related Genes in Sjögren's Syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune multifactorial disease characterized by inflammation and lymphocytic infiltration of the exocrine glands. Several studies have highlighted the involvement of oxidative stress in this pathology, suggesting that it could induce mitochondrial dysfunctions. Mitochondria could have a role in inflammatory and immune processes.

Impact of , and Genetic Polymorphisms in the Response to TNF-i Treatment in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease. The introduction of therapy with biological drugs is promising, even if the efficacy is very variable. Since the response to drugs is a complex trait, identifying genetic factors associated to treatment response could help define new biomarkers for a more effective and personalized therapy.

Late-onset neonatal sepsis: genetic differences by sex and involvement of the NOTCH pathway.

Background: Late-Onset Neonatal Sepsis (LOS) is a rare condition, involving widespread infection, immune disruption, organ dysfunction, and often death. Because exposure to pathogens is not completely preventable, identifying susceptibility factors is critical to characterizing the pathophysiology and developing interventions. Prior studies demonstrated both genetics and infant sex influence susceptibility.

The Impacts of the Clinical and Genetic Factors on Chronic Damage in Caucasian Systemic Lupus Erythematosus Patients.

Objective: The purpose of this study was to determine the distribution of organ damage in a cohort of systemic lupus erythematosus (SLE) patients and to evaluate the roles of clinical and genetic factors in determining the development of chronic damage. Methods: Organ damage was assessed by the SLICC Damage Index (SDI). We analyzed a panel of 17 single-nucleotide polymorphism (SNPs) of genes already associated with SLE, and we performed a phenotype−genotype correlation analysis by evaluating specific domains of the SDI.

A multilocus genetic study evidences the association of autoimmune-related genes with Psoriatic Arthritis in Italian patients.

Psoriatic Arthritis (PsA) is an immune-mediated rheumatic disease caused by the interaction between environmental factors and genetic predisposition. Many of the risk loci associated with PsA susceptibility are shared with other autoimmune diseases, suggesting an involvement of the same pathways in these diseases. We investigated the association between nine selected polymorphisms and PsA susceptibility and their possible role in the modulation of the disease activity.

Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population.

Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three most common eating disorders (EDs). Their etiopathogenesis is multifactorial where both the environmental and genetic factors contribute to the disease outcome and severity. Several polymorphisms in genes involved in the dopaminergic pathways seem to be relevant in the susceptibility to EDs, but their role has not been fully elucidated yet.

VDR Polymorphisms in Autoimmune Connective Tissue Diseases: Focus on Italian Population.

Vitamin D is an important hormone involved in various physiologic processes, and its activity is linked to binding with vitamin D receptor (VDR). Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and, consequently, alter the effects of vitamin D. Variants in VDR gene have been associated with susceptibility to many illnesses sensitive to vitamin D administration and to autoimmune disorders, but no data are available regarding autoimmune connective tissue diseases in Italian population.

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations.

Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called "non-radiographic axial SpA" (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi).

Emerging Role of microRNAs and Long Non-Coding RNAs in Sjögren's Syndrome.

Sjögren's Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic regulations represent a link between genetic predisposition and environmental factors.

mRNA expression analysis confirms CD44 splicing impairment in systemic lupus erythematosus patients.

Background: Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44.

Altered expression of miR-142, miR-155, miR-499a and of their putative common target in systemic lupus erythematosus.

To evaluate genetic and expression variability of three miRNAs potentially involved in systemic lupus erythematosus (SLE) and to identify any miRNA's target gene. Gene polymorphisms and expression levels of three miRNAs have been evaluated in a cohort of SLE patients and controls. miR-142 and miR-499a were significantly down-expressed in patients (p = 0.

CLEC4E (Mincle) genetic variation associates with pulmonary tuberculosis in Guinea-Bissau (West Africa).

Tuberculosis (TB) is the leading cause of death from a single infectious agent. According to the WHO, 85% of cases in 2018 were pulmonary tuberculosis (PTB), making it the most prevalent form of the disease. Although the bacillus responsible for disease, Mycobacterium tuberculosis (MTB), is estimated to infect 1.

Expression study of candidate miRNAs and evaluation of their potential use as biomarkers of diabetic neuropathy.

To evaluate the expression of candidate miRNAs in relation to diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). The expression of six candidate miRNAs has been evaluated in 49 Type 2 diabetes patients with neurological evaluation. A higher expression of miR-128a was seen in patients with DPN compared with those without DPN (p = 0.

Mitochondrial DNA Copy Number in Peripheral Blood Is Reduced in Type 2 Diabetes Patients with Polyneuropathy and Associated with a Gene Polymorphism.

Our aim was to evaluate in a cohort of 125 Italian patients with type 2 diabetes (T2D), who underwent neurological evaluation, the possible differences in the number of mitochondrial DNA copies (mtDNA) comparing positive and negative patients for cardiovascular autonomic neuropathy (CAN) or diabetic peripheral neuropathy (DPN) and comparing them with healthy controls. We also investigated a possible correlation of the number of mtDNA copies with the polymorphism rs3746444 of the . T2D patients show a decrease in the number of mtDNA copies compared to healthy controls ( = 2 × 10).