Dataset Information

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies.

ABSTRACT: Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4, TNFAIP3-OLIG3, and TRAF1/C5. Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. This review will summarize the genetic factors that have been implicated in the pathogenesis of RA, and how these determinants may factor into the potential pharmacogenetics of this disease. We will also review the therapeutic agents that are currently being utilized or presently being evaluated in the treatment of RA, along with potential pharmacogenetic markers that have been proposed for such medications.

SUBMITTER: O'Rielly DD

PROVIDER: S-EPMC3513198 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies.

O'Rielly Darren D DD Rahman Proton P

Pharmacogenomics and personalized medicine 20100330

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTP ...[more]

PMID: 23226040

Similar Datasets

Project description:This research aims at assessing the m6A methylome in the RA peripheral blood mononuclear cells (PBMCs) and perform potential drug targets prediction analysis. Five RA samples and ten control samples were obtained from China-Japan Friendship Hospital. The various expression of m6A methylation and genes in RA and control group were compared with methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). Bioinformatics explorations were also made to explore the enriched biological roles and paths of the differentially expressed m6A methylation and genes. Potential drug targets prediction and validation were also constructed to provide potential therapeutic targets for RA. In total, 583 dysregulated m6A peaks, of which 295 were greatly upregulated and 288 were greatly downregulated, were identified. Similarly, 1570 differentially genes were acquired by RNA-seq, including 539 upregulated and 1031 downregulated. According to deeper joint exploration, the m6A methylation and mRNA expression degrees of 35 genes varied greatly, of which including 13 hyper-methylated as well as upregulated genes (hyper-up), 12 hyper-methylated and downregulated genes (hyper-down), 5 hypo-methylated as well as upregulated genes (hypo-up), and 5 hypo-methylated and downregulated genes (hypo-down) GO and KEGG explorations showed the enrichment of these distinct genes in “protein transport” “protein binding” and “lysosome”. In addition, the mRNA levels of TUBB2A, IGF2BP3, DYNC1I1 and FOSL1 were increased and consistent with the trend of our sequencing results. While after the treatment of TP and MTX, their mRNA levels were decreased. This research set up the transcriptional map of m6A in RA PBMCs and displayed the hidden association between RNA methylation alternation and associated genes in RA. The outcomes highlight the importance of m6A modification as a gene regulatory system in RA. Furthermore, TUBB2A, IGF2BP3, DYNC1I1 and FOSL1 might be potential therapeutic targets of TP and MTX during RA treatment.

Dataset Information

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies.

Publications

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets