Single nucleotide polymorphism of osteoprotegerin as a possible biomarker of rheumatoid arthritis in Bashkir population of Chelyabinsk region

Abstract

Rheumatoid arthritis (RA) is a multifactorial autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis. The protein osteoprotegerin (OPG) is a member of bone tissue homeostasis (RANK/RANKL/OPG) which is responsible for the regulation of osteoclast differentiation and osteolysis. The altered binding of RANKL and OPG is one of the causes of many diseases with increased production of pro-inflammatory cytokines, including rheumatoid arthritis. Polymorphic variants of the genes that control protective reactions could affect the level of production for encoded proteins and, thus, changing the course of immune response in RA. G1181C SNP in osteoprotegerin gene leads to disruption of its transcriptional activity and conformation of the protein itself, which can lead to an imbalance of pro- and anti-inflammatory cytokines. We analyzed the relationship between the TNFRSF11B gene polymorphism at the 1181 G C position and the risk of developing RA in the Bashkir population. The analysis was based on a molecular genetic study of single nucleotide polymorphism in groups of patients with rheumatoid arthritis and conditionally healthy individuals of the Bashkir population of the Chelyabinsk Region. Statistical evaluation was carried out using standard criteria generally accepted in immunogenetics. The 1181*GC polymorphism of the osteoprotegerin gene is characterized by interpopulation differences, which confirms the importance of using an ethnically identical comparison group to assess the association with a predisposition to multifactorial pathology. We showed that the carriage of genotype 1181 G/C was increased in the group of Bashkirs with rheumatoid arthritis. This genotype could be considered a biomarker of susceptibility to RA. No differences in the SNP allelic frequencies and genotypes were found among women with RA. Our research is a part of comprehensive assessment of the interaction of cytokines and their receptors from the TNFαsuperfamily as an immunogenetic component of RA genesis.