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Abstract
Objective: To investigate the possible association between polymorphisms [the −2510A/G promoter polymorphism (rs1024611) and the Cys35Cys coding polymorphism (rs4586) in exon 2] of the chemokine (C–C motif) ligand 2 (CCL2) gene and knee osteoarthritis (OA) in a Korean population.
Methods: DNA was obtained from 153 Korean primary knee OA patients and 270 healthy controls. CCL2 genomic variants (−2510A/G and Cys35Cys polymorphisms) were detected by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). In additional, the effect of −2510A/G on CCL2 transcription was examined, using a luciferase reporter gene construct transfected into HMC‐1 cells.
Results: The −2510A/G promoter polymorphism was associated with OA [genotype frequency, p = 0.041; allele frequency, p = 0.017, odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.07–1.96]. Significant association was observed between the G carrier of the −2510A/G promoter polymorphism and primary knee OA patients (p = 0.021, OR = 2.25, 95% CI = 1.12–4.52). The G carrier of the −2510A/G promoter polymorphism was also associated with both clinically subtyped OA patients (OA patients with functionally poor index and radiographically severe OA patients). However, no significant difference was found in the Cys35Cys polymorphism. Haplotype frequency analysis revealed a significant difference (χ2 = 8.98, p = 0.030). The CCL2 serum level of subjects with the G carrier (290.0±87.5 pg/mL) of the −2510A/G promoter polymorphism was statistically higher than that of subjects with the non‐G carrier (161.5±48.3 pg/mL). The luciferase activity was significantly greater from interleukin (IL)‐1β‐induced cells transfected with constructs containing G at position −2510.
Conclusions: The G carrier of the −2510A/G promoter polymorphism was found to be associated with primary knee OA, and could be a susceptibility factor in the development of primary knee OA in the Korean population.