INNATE IMMUNITY AND PRO-INFLAMMATORY CYTOKINE GENE VARIANTS AS DETERMINANTS OF SUBCLINICAL ATHEROSCLEROSIS IN RHEUMATOID ARTHRITIS

Abstract

Rheumatoid arthritis (RA) is associated with a 1.5–2-fold increase in cardiovascular morbidity and mortality compared to the general population, representing the leading cause of premature death in RA patients [1]. The mechanisms underlying accelerated atherosclerosis include systemic inflammation, endothelial dysfunction and shared genetic predisposition with autoimmunity. Toll-like receptor 4 (TLR4) recognizes both pathogen-associated and damage-associated molecular patterns; two functional polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are commonly inherited in linkage disequilibrium and modulate ligand recognition [3, 6]. Tumor necrosis factor alpha (TNF-α) plays a central role in RA pathogenesis through activation of NF-κB signaling [2, 7]. Despite extensive characterization of TLR4 and TNF-α polymorphisms in RA susceptibility, their joint contribution to cardiovascular comorbidity in Central Asian populations remains insufficiently explored [5].