Association of IL-6, IL-8, MMP-13 gene polymorphisms with knee osteoarthritis susceptibility in the Chinese Han population

Abstract

<b>Objective:</b> To identify the association between the interleukin (IL) 6 (<i>IL-6</i>) rs1800795 (-174 G>C), <i>IL-8</i> rs4073 (-251T>A), and matrix metalloproteinase-13 (<i>MMP-13</i>) rs2252070 (-77G>A) gene polymorphisms and knee osteoarthritis (KOA) susceptibility in the Chinese Han population. <b>Methods:</b> Genomic DNA was extracted from a total of 400 KOA patients and 400 healthy subjects. Sanger sequencing was performed to determine the genotypes of the <i>IL-6</i> rs1800795 (-174 G/C), <i>IL-8</i> rs4073 (-251A/T), and <i>MMP-13</i> rs2252070 (-77A/G) loci. The mRNA expression levels of <i>IL-6, IL-8</i>, and <i>MMP-13</i> in osteoblasts and the protein expression levels of IL-6, IL-8, and MMP-13 in the synovial fluids of KOA patients were analyzed. <b>Results:</b> The recessive model of IL-6 rs1800795 locus was found to be associated with KOA risk (adjusted odds ratio (OR) = 1.657, 95% confidence interval (CI) = 1.396-1.866, <i>P</i><0.001). The <i>IL-8</i> rs4073 locus dominant and recessive model showed no significant association with KOA risk (<i>P</i>>0.05). The dominant and recessive models of the <i>MMP-13</i> rs2252070 locus showed higher risk for developing KOA (dominant model: adjusted OR = 1.271, 95%CI = 1.095-1.480, <i>P</i>=0.001; recessive model: adjusted OR = 1.361 95%CI = 1.151-1.569, <i>P</i><0.001). The G>C mutation in IL-6 rs1800795 and the G>A mutation in <i>MMP-13</i> rs2252070 were associated with significantly higher KOA disease severity. The G>C mutation in the IL-6 rs1800795 locus was associated with up-regulation of IL-6 expression. The G>A mutation in the <i>MMP-13</i> rs2252070 locus was associated with up-regulation of MMP-13 expression. <b>Conclusion:</b> The <i>IL-8</i> rs4073 (-251T>A) mutation was not associated with KOA susceptibility. The <i>IL-6</i> rs1800795 (-174 G>C) and <i>MMP-13</i> rs2252070 (-77G>A) mutations were associated with KOA susceptibility, increased disease severity, and up-regulation of IL-6 and MMP-13 expression levels.