Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Abstract

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

“…More than a hundred loci are associated with RA risk, most of which involve immune mechanisms [ 70 ]. The human leukocyte antigen (HLA) system, specifically HLA-DRB1 seems to be the most dominant, and it is related to peptide (and self-peptide) binding in pathogenesis [ 71 ].…”

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“…Its clinical manifestation is multiple arthritis of the small joints of the hands and feet, which can lead to joint pain, injury and even loss of function, and seriously affects the quality of life of patients [39]. At present, the pathogenesis of rheumatoid arthritis is not very clear, but most studies believe that T lymphocytes and macrophages release a large number of in ammatory cytokines to cause bone and joint damage in rheumatoid arthritis [40].…”

Cognitive Decline in Rheumatoid Arthritis: Insight into the Molecular Pathogenetic Mechanisms

“…A complex interaction between genotype and exposure to environmental factors (cigarette smoking, air pollutants, and occupational dust) is likely to determine the onset and development of RA [ 5 ]. Genetic studies have found an association of more than 100 polymorphisms with RA, mainly in the major histocompatibility complex (MHC) locus, but also in genes encoding for cytokines/chemokines and their receptors, components of intracellular signaling pathways, and costimulatory factors [ 6 ]. The implication of genetic factors in the RA pathogenesis is demonstrated by a positive family history, which increases the risk of RA by about three to five times [ 4 , 7 ].…”