Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital 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. Non-HLA genes, i.e. tumour necrosis factor-α (TNF-α) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF-α gene, the data published so far indicate the possible existence of TNF-α gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 (PADI4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), signal transducer and activator of transcription (STAT4), cluster of differentiation 244 (CD244) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease.

• Authors: Vasanth Konda Mohan, Nalini Ganesan, Rajasekhar Gopalakrishnan
• Journal: Journal of genetics (J Genet) Vol. 93 Issue 2 Pg. 597-605 (Aug 2014) ISSN: 0973-7731 [Electronic] India
• PMID: 25189266 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Autoantibodies
• Biomarkers
• Genetic Markers
• HLA Antigens

Topics

• Animals
• Arthritis, Rheumatoid (blood, genetics, immunology)
• Autoantibodies (blood)
• Biomarkers (blood)
• Genetic Association Studies
• Genetic Markers
• Genetic Predisposition to Disease
• HLA Antigens (genetics)
• Humans
• Polymorphism, Genetic
• Risk Factors