Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetics of systemic sclerosis: an update.

ABSTRACT: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune cell activation, and fibrosis of the skin and internal organs. Over the past few years, a role for genetics in the susceptibility for SSc has been established. This review aims to provide an update on the progress made in the past year or so within the field of SSc genetics research. This year has been of particular interest due to the publication of a large genome-wide association study, further investigations into gene-gene interactions, and the tendency to validate genetic results in functional models.

SUBMITTER: Broen JC

PROVIDER: S-EPMC3253992 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genetics of systemic sclerosis: an update.

Broen Jasper C A JC Coenen Marieke J H MJ Radstake Timothy R D J TR

Current rheumatology reports 20120201 1

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune cell activation, and fibrosis of the skin and internal organs. Over the past few years, a role for genetics in the susceptibility for SSc has been established. This review aims to provide an update on the progress made in the past year or so within the field of SSc genetics research. This year has been of particular interest due to the publication of a large genome-wide association study, further investigatio ...[more]

PMID: 22102179

Similar Datasets

Genetics of systemic sclerosis.

Project description:Systemic sclerosis is an autoimmune disease characterized by generalized fibrosis in connective tissues and internal organs as consequences of microvascular dysfunction and immune dysfunctions, which leads to premature death in affected individuals. The etiology of systemic sclerosis is complex and poorly understood, but as with most autoimmune diseases, it is widely accepted that both environmental and genetic factors contribute to disease risk. During the last decade, the number of genetic markers convincingly associated with systemic sclerosis has exponentially increased. In this article, we briefly mention the genetic components of systemic sclerosis. Then, we review the classical and novel genetic associations with systemic sclerosis, analyzing the firmest and replicated signals within non-human leukocyte antigen genes, identified by both candidate gene approach and genome-wide association studies. We also provide an insight into the future perspectives that will shed more light into the complex genetic background of the disease. Despite the remarkable advance of systemic sclerosis genetics during the last decade, the use of the new genetic technologies such as next-generation sequencing, as well as the deep phenotyping of the study cohorts, to fully characterize the genetic component of this disease is imperative to identify causal variants, which leads to more targeted and effective treatment of systemic sclerosis.

| S-EPMC8922623 | biostudies-literature

Genetics of amyotrophic lateral sclerosis: an update.

Project description:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving both upper motor neurons (UMN) and lower motor neurons (LMN). Enormous research has been done in the past few decades in unveiling the genetics of ALS, successfully identifying at least fifteen candidate genes associated with familial and sporadic ALS. Numerous studies attempting to define the pathogenesis of ALS have identified several plausible determinants and molecular pathways leading to motor neuron degeneration, which include oxidative stress, glutamate excitotoxicity, apoptosis, abnormal neurofilament function, protein misfolding and subsequent aggregation, impairment of RNA processing, defects in axonal transport, changes in endosomal trafficking, increased inflammation, and mitochondrial dysfunction. This review is to update the recent discoveries in genetics of ALS, which may provide insight information to help us better understanding of the disease neuropathogenesis.

| S-EPMC3766231 | biostudies-literature

Updates on genetics in systemic sclerosis.

Project description:Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.

| S-EPMC8204536 | biostudies-literature

Genetics, Epigenetics, and Genomics of Systemic Sclerosis.

Project description:Systemic sclerosis (SSc) is a complex autoimmune disease that occurs in a genetically susceptible host. Genetic studies performed so far reveal that multiple genetic loci contribute to disease susceptibility in SSc. The purpose of this review is to discuss the current knowledge of genetics in SSc by exploring the observational evidence, the different genetic studies, and their modalities as well as the most relevant genes discovered by these. The importance of gene expression variation and the different mechanisms that govern it, including the recently discovered field of epigenetics, are also explored, with an emphasis on microRNA.

| S-EPMC4515564 | biostudies-literature

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma.

Project description:Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.

| S-EPMC7545907 | biostudies-literature

An update on the pharmacotherapeutic options and treatment strategies for systemic sclerosis.

Project description:IntroductionSystemic sclerosis (SSc) is a multi-dimensional connective tissue disease of unknown etiology. Given the immense clinical complexity of SSc, the treatment of this condition is not standardized and considerable heterogeneity exists in SSc management approaches. The purpose of this article is to highlight novel therapeutic strategies and new medications under development for the treatment of systemic sclerosis (SSc).Areas coveredHerein, the authors focus primarily on recently completed clinical trials and phase 3 and 4 clinical trials of therapeutic agents that show promise in SSc. This review is organized by the clinical complications that occur in SSc, for which novel treatment strategies are under study.Expert opinionCombining therapies to address the individual manifestations of SSc is a cornerstone to the comprehensive management of this condition. Therapeutic strategies must take into account the organs involved, the level of disease activity in each area, and the disease stage. Controlling the complex biological network, progressive vasculopathy and fibrosis, as well as manifestations of end-organ dysfunction are all critical considerations when determining the best treatment approach for SSc.

| S-EPMC7913471 | biostudies-literature

Update on the Genetics of Systemic Lupus Erythematosus: Genome-Wide Association Studies and Beyond.

Project description:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.

| S-EPMC6829439 | biostudies-literature

Recent advances in the genetics of systemic sclerosis: toward biological and clinical significance.

Project description:Significant advances have been made in understanding the genetic basis of systemic sclerosis (SSc) in recent years. Genomewide association and other large-scale genetic studies have identified 30 largely immunity-related genes which are significantly associated with SSc. We review these studies, along with genomewide expression studies, proteomic studies, genetic mouse models, and insights from rare sclerodermatous diseases. Collectively, these studies have begun to identify pathways that are relevant to SSc pathogenesis. The findings presented in this review illustrate how both genetic and genomic aberrations play important roles in the development of SSc. However, despite these recent discoveries, there remain major gaps between current knowledge of SSc, a unified understanding of pathogenesis, and effective treatment. To this aim, we address the important issue of SSc heterogeneity and discuss how future research needs to address this in order to develop a clearer understanding of this devastating and complex disease.

| S-EPMC4361757 | biostudies-literature

Stroke Genetics Update: 2011.

Project description:Although stroke remains a leading cause of disability and mortality worldwide, recently there have been significant advances related to our understanding of the genetic basis of stroke. Ongoing research efforts put us on the cusp for major breakthroughs in the field. In this review, we present the substantial evidence for the contribution of genetic variation to the development of stroke, and the difficulties posed in the study of stroke given the numerous genetically driven risk factors and stroke subtypes. We emphasize recent findings implementing candidate gene and genome-wide association approaches. We then discuss how emerging knowledge is informing and reshaping our understanding of stroke biology and how, in the near term, genetics may be used clinically to identify individuals who are at risk of disease or who may derive benefit from specific treatment modalities. Lastly, we address ongoing and future approaches that will continue to improve our understanding of stroke genetics.

| S-EPMC3234118 | biostudies-literature

B-cell depletion therapy in systemic sclerosis: experimental rationale and update on clinical evidence.

Project description:Systemic sclerosis (SSc) is a systemic rheumatic disease with poor prognosis since therapeutic options are limited. Recent evidence from animal models suggests that B-cells may be actively involved in the fibrotic process. B-cells from tight skin mice, an animal model of scleroderma, display a "hyperresponsive" phenotype; treatment with rituximab (RTX) significantly attenuates skin fibrosis in this animal model. In humans, B-cell infiltration is a prominent finding in most lung biopsies obtained from patients with SSc-associated interstitial lung disease. Several open label studies have assessed the clinical efficacy of RTX in SSc. In most patients skin fibrosis improved; lung function either improved or remained stable. Definite conclusions regarding the clinical efficacy of RTX in SSc cannot be drawn but further exploration with a multicenter, randomized study is warranted.

| S-EPMC3150146 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data