AB1291 ASSOCIATION OF CCL2 GENE POLYMORPHISMS AND THEIR SERUM LEVELS WITH SUSCEPTIBILITY TO KNEE OSTEOARTHRITIS
Authors: Amar Chandra Sharma, Rajeswar Nath Srivastava, Sudeepti Srivastava, Saloni Raj
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Osteoarthritis (OA) is one of the most depleting chronic disorders and its pathogenesis is yet to be unfold. It is characterized by pain, swelling, stiffness, decreased ability to move and, sometimes, the formation of bone spurs. Knee Osteoarthritis (KOA) is multifactorial and remains largely understudied at molecular level. The available literature suggested that the development, onset and progression of OA is significantly affected by genetic factors. Chemokines are small, secreted proteins that released from chondrocytes and/or synovial fibroblasts of KOA patients. In this case control study, we investigated the possible association between promoter polymorphisms rs1024611 and the polymorphism rs4586 in exon 2 of the chemokine (C–C motif) ligand 2 (CCL2) gene and knee OA. <h3>Objectives:</h3> To investigate the possible association between promoter polymorphisms rs1024611 and the polymorphism rs4586 in exon 2 of the CCL2 gene and KOA. <h3>Methods:</h3> DNA was obtained from 300 primary knee OA patients and 300 healthy controls. CCL2 genomic variants (rs1024611 and rs4586 polymorphisms) were detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). In additional, the effect of serum levels of rs1024611 and rs4586 on cases and controls were examined by enzyme-linked immunosorbent assay (ELISA). <h3>Results:</h3> The rs1024611 A/G promoter polymorphism was associated with KOA [genotype frequency, p= 0.007; allele frequency, p= 0.01]. Significant association was observed between the G carrier of the rs1024611 A/G promoter polymorphism and primary knee OA patients (p=0.01). However, no significant difference was found in the rs4586 polymorphism. Haplotype frequency analysis revealed a significant difference (x<sup>2</sup>= 8.01, p= 0.02). The CCL2 serum level of subjects with the G carrier (285.0 ± 86.5 pg/mL) of the rs1024611 A/G promoter polymorphism was statistically higher than that of subjects with the non-G carrier (160.5±47.8 pg/mL). Further in relation with clinical severity of KOA, we observed signification association of the G carrier of the rs1024611 A/G promoter polymorphism with both Visual analogue scale (VAS) (p&lt;0.01) and Western Ontario and McMaster Universities (WOMAC) score (p&lt;0.05). <h3>Conclusion:</h3> The G carrier of the rs1024611 A/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 North Indian population. <h3>References</h3> [1] Hulin-Curtis SL, Bidwell JL &amp; Perry MJ. Association between CCL2 haplotypes and knee osteoarthritis. International journal of Immunogenetics.2015 [2] Park HJ, Yoon SH, Zheng LT, Lee KH, Kim JW, Chung JH, Lee YA, Hong SJ: Association of the 22510A/G chemokine (C–C motif) ligand 2 polymorphism with knee osteoarthritis in a Korean population. Scand J Rheumatol 2007;36:299–306 <h3>Disclosure of Interests:</h3> None declared