The Association of Sdf-1 and Cxcr4 Gene Polymorphisms With Rheumatoid Arthritis Susceptibility in the Iranian Population Publisher



Aghaei S¹ ; Sahamifard MH² ; Gharibi S² ; Feizi L¹ ; Farashahiyazd E¹ ; Mahmoudi M³ ; Shahvazian E² ; Mahmoudi MB² ; Nikkhah H¹ ; Akhlaghi M³
Source: Human Gene Published:2025

Abstract

Background: Stromal cell-derived factor-1 (SDF-1) and CXC motif chemokine receptor 4 (CXCR4) play critical roles in the pathogenesis of rheumatoid arthritis (RA) by regulating immune cell migration and inflammatory responses. This study investigates the association of SDF-1 and CXCR4 gene polymorphisms with the risk of developing RA in an Iranian population. Methods: The study comprised 93 patients with RA and 98 gender- and age-matched healthy controls. The genotypes of SDF-1 G801A (rs1801157) and CXCR4 C138T (rs2228014) were detected using the restriction fragment length polymorphism (RFLP) and amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. Results: A significant reduction in susceptibility to RA was associated with the SDF-1 G801A polymorphism in homozygous individuals (OR = 0.383; 95 % CI = 0.165–0.888) and in recessive models (OR = 0.418; 95 % CI = 0.185–0.946). In contrast, the CXCR4 C138T variant was linked to an increased susceptibility to RA in the recessive model (OR = 2.557; 95 % CI = 1.024–6.384). Therefore, the SDF-1 polymorphism may confer a protective effect against RA, while the CXCR4 polymorphism may heighten the risk of developing the condition. Conclusion: This is the first study in an Iranian population demonstrating these associations. Our results indicate that genetic variations in SDF-1 and CXCR4 may significantly influence RA susceptibility. © 2025 Elsevier B.V.