Association of the 22510A/G chemokine (C-C motif) ligand 2 polymorphism with knee osteoarthritis in a Korean population

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 reactionrestriction fragment length polymorphism (PCR- RFLP). In additional, the effect of 22510A/ G on CCL2 transcription was examined, using a luciferase reporter gene construct transfected into HMC-1 cells. Results: The 22510A/ 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 22510A/ 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 22510A/ 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 (chi(2) =8.98, p=0.030). The CCL2 serum level of subjects with the G carrier ( 290.0 +/- 87.5 pg/ mL) of the 22510A/ 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)-1 beta- induced cells transfected with constructs containing G at position-2510. Conclusions: The G carrier of the 22510A/ 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.