SMAD3 Gene Polymorphisms and Protein Expression as Potential Biomarkers of Susceptibility to Knee Osteoarthritis

Background Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage degradation, joint pain, stiffness, and functional disability. Genetic susceptibility plays a significant role in the pathogenesis of OA. SMAD3, an important intracellular mediator of the transforming growth factor-beta (TGF-β) signaling pathway, has been implicated in cartilage homeostasis and in the progression of OA. This study evaluates the association of SMAD3 gene polymorphisms SmaI (C/T; rs6494629) and FokI (A/C; rs2289263) with susceptibility to knee OA and analyzes the protein expression of SMAD3 in serum and cartilage tissue. Materials and methods A hospital-based case-control study was conducted involving 200 clinically diagnosed OA patients and 200 healthy controls. Demographic, anthropometric, clinical, and radiological data were recorded. Genomic DNA was isolated from peripheral blood samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping of SMAD3 polymorphisms. SMAD3 protein expression was analyzed in serum using ELISA and in cartilage tissue using western blotting. Results Significant associations were observed between SMAD3 polymorphisms and OA susceptibility. For rs6494629, CT and TT genotypes were significantly associated with increased OA risk compared to the CC genotype (p = 0.009 and p = 0.013, respectively). For rs2289263, CA and CC genotypes showed increased susceptibility to OA (p = 0.02 and p = 0.044, respectively). Serum and tissue SMAD3 expression levels were elevated in OA patients compared to controls. Conclusion Altered expression of SMAD3 protein may contribute to OA pathogenesis and could serve as a potential biomarker for disease susceptibility and progression.