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Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies
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 antig...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513198/ https://www.ncbi.nlm.nih.gov/pubmed/23226040 |
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author | O’Rielly, Darren D Rahman, Proton |
author_facet | O’Rielly, Darren D Rahman, Proton |
author_sort | O’Rielly, Darren D |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3513198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35131982012-12-05 Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies O’Rielly, Darren D Rahman, Proton Pharmgenomics Pers Med Review 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. Dove Medical Press 2010-03-30 /pmc/articles/PMC3513198/ /pubmed/23226040 Text en © 2010 O’Rielly and Rahman, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Review O’Rielly, Darren D Rahman, Proton Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title | Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title_full | Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title_fullStr | Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title_full_unstemmed | Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title_short | Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies |
title_sort | pharmacogenetics of rheumatoid arthritis: potential targets from susceptibility genes and present therapies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513198/ https://www.ncbi.nlm.nih.gov/pubmed/23226040 |
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