Association of cytokine gene polymorphisms with osteoarthritis susceptibility

Abstract

Osteoarthritis (OA) is a multifactorial disease characterized by low-grade inflammatory processes that are mediated initially by the cells and factors of the innate immune system. In addition to their key role in inflammation, cytokines contribute to the pathogenesis of OA through angiogenesis and chemotaxis. The purpose of the present case-control study was to investigate a possible association of four cytokine single nucleotide polymorphisms (SNPs), IL-4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from blood samples collected from 305 Romanian subjects (90 patients with OA and 215 controls) and the genotyping of the SNPs was performed by TaqMan allelic discrimination polymerase chain reaction using predesigned assays. Our data indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21-3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI, 1.17-3.17; P=0.009) in a dominant model. The association remained significant only for knee OA in the subgroups analysis. No correlations were observed between the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768 SNP could contribute to OA susceptibility in the Romanian population, providing novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.

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“…So far, genome‐wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) in a range of genes, such as growth differentiation factor 5 gene, Frizzled‐related protein gene, cartilage oligomeric matrix protein gene and chondroadherin‐like gene, and fat mass and obesity‐associated gene, are associated with susceptibility to OA. Apart from that, increasing literature elucidated a vital role of inflammation during the pathogenesis of OA, and various inflammatory cytokine genes which conferred susceptibility to OA are still being investigated . Among those inflammation‐related genes, evidence has been published for the association of interleukin‐17 ( IL‐17 ) SNPs and OA predisposition.…”

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