Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
Laboratory of Epigenetics, Research Centre for Medical Genetics, 115478 Moscow, Russia.
Int J Mol Sci. 2020 Jul 11;21(14):4911. doi: 10.3390/ijms21144911.
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.
类风湿关节炎（RA）是全球最常见的炎症性关节病。RA 的可能表现可以由广泛的症状、临床形式和病程选择来代表。这种多因素疾病是由遗传易感性和环境因素引发的。临床和家系研究都表明疾病在家族中积累。揭示候选基因错义变异对疾病病程的影响，阐明了对 RA 分子发病机制的理解。基于多变量全基因组关联研究（GWAS）的分析确定了参与疾病发病机制的基因和信号通路。然而，这些确定的 RA 候选基因变异仅解释了 30%的家族性疾病病例。到目前为止，还没有确定导致相当一部分家族性 RA 的遗传原因。因此，确定不同人群中的 RA 风险群体以及某些遗传变异对疾病发展、进展和治疗的可能预后价值非常重要。我们的综述有两个目的。首先，总结 RA 候选基因的数据以及这些等位基因在不同人群中增加疾病风险的情况。其次，描述如何将遗传变异用于 RA 治疗药物的选择。
