The genetic puzzle of rheumatoid arthritis: Causes, progression, and treatment

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and progressive joint destruction, influenced by a complex interplay of genetic and environmental factors. Substantial evidence highlights a significant genetic contribution to RA pathogenesis, with key genetic risk factors including human leukocyte antigen (HLA) genes and non-HLA variants. These genetic elements are intricately involved in immune dysregulation, antigen presentation, and signaling pathways. The genetic heterogeneity of RA is further accentuated by gene-gene and gene-environment interactions, while biomarkers and genetic profiles associated with disease progression and joint damage continue to be rigorously explored. Additionally, the evolving field of pharmacogenomics sheds light on the challenges and prospects of developing personalized therapeutic approaches for RA. Genetic markers are being explored to predict response to various RA therapies, including DMARDs and biologics. Understanding genetic risk factors and pharmacogenomic insights can support early diagnosis, predict disease severity and progression, and improve therapeutic decisions in RA patients. The main objective of this review is to comprehensively explore current knowledge regarding the genetic factors contributing to RA susceptibility, progression, and treatment response. Furthermore, by addressing genetic risk factors, gene-environment interactions, and emerging pharmacogenomic insights, the review aims to highlight critical gaps and future directions in genetic researches related to RA.