**Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response**

**Dmitry S. Mikhaylenko 1,2,\*, Marina V. Nemtsova 1,2, Irina V. Bure 1, Ekaterina B. Kuznetsova 1,2, Ekaterina A. Alekseeva 1,2, Vadim V. Tarasov 3, Alexander N. Lukashev 1,4, Marina I. Beloukhova 1, Andrei A. Deviatkin <sup>1</sup> and Andrey A. Zamyatnin, Jr. 1,5,\***


Received: 17 June 2020; Accepted: 9 July 2020; Published: 11 July 2020

**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.

**Keywords:** rheumatoid arthritis; polymorphism; genetic predisposition; mutation; methotrexate; interleukin; targeted therapy
