Abstract
Objective: To identify the association between the interleukin (IL) 6 (IL-6) rs1800795 (-174 G>C), IL-8 rs4073 (-251T>A), and matrix metalloproteinase-13 (MMP-13) rs2252070 (-77G>A) gene polymorphisms and knee osteoarthritis (KOA) susceptibility in the Chinese Han population. Methods: 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 IL-6 rs1800795 (-174 G/C), IL-8 rs4073 (-251A/T), and MMP-13 rs2252070 (-77A/G) loci. The mRNA expression levels of IL-6, IL-8, and MMP-13 in osteoblasts and the protein expression levels of IL-6, IL-8, and MMP-13 in the synovial fluids of KOA patients were analyzed. Results: 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, P<0.001). The IL-8 rs4073 locus dominant and recessive model showed no significant association with KOA risk (P>0.05). The dominant and recessive models of the MMP-13 rs2252070 locus showed higher risk for developing KOA (dominant model: adjusted OR = 1.271, 95%CI = 1.095–1.480, P=0.001; recessive model: adjusted OR = 1.361 95%CI = 1.151–1.569, P<0.001). The G>C mutation in IL-6 rs1800795 and the G>A mutation in MMP-13 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 MMP-13 rs2252070 locus was associated with up-regulation of MMP-13 expression. Conclusion: The IL-8 rs4073 (-251T>A) mutation was not associated with KOA susceptibility. The IL-6 rs1800795 (-174 G>C) and MMP-13 rs2252070 (-77G>A) mutations were associated with KOA susceptibility, increased disease severity, and up-regulation of IL-6 and MMP-13 expression levels.
Highlights
The recessive model of IL-6 rs1800795 locus was associated with high risk for knee osteoarthritis (KOA), and the rs1800795 locus C allele was a strong risk factor for KOA (Table 3)
The dominant and recessive models of the matrix metalloproteinase-13 (MMP-13) rs2252070 were found to be associated with high risk for KOA (Table 3)
Our findings showed that the IL-8 rs4073 (-251T>A) mutation was not associated with KOA susceptibility and disease severity
Summary
A total of 400 patients with KOA undergoing artificial joint replacement surgery at Zhejiang Provincial People’s Hospital from May 2014 to May 2017 were recruited in the case group. The case group comprised 184 males and 216 females who were 25–81 years old, with an average age of 56.6 +− 9.3. A total of 400 healthy subjects were recruited in the control group. The control group comprised 189 males and 211 females who were 27–80 years old, with an average age of 55.7 +− 10.5. X-ray analysis confirmed the absence of KOA or other types of arthritis and no evident symptoms of joint pain, including pain, swelling, tenderness, and limited mobility. The present study was approved by the Medical Ethics Committee of Zhejiang Provincial People’s Hospital.
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