title: 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.affiliation: Department of Biochemistry, Sri Ramachandra University, Porur, Chennai 600 116, India. nalinisrmc@gmail.com.
authors.forename: Vasanth Konda
authors.initials: VK
authors.lastname: Mohan
authors.forename: Nalini
authors.initials: N
authors.lastname: Ganesan
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Gopalakrishnan
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D005819:Genetic Markers; D006680:HLA Antigens