Department of Spinal Surgery, Qingdao Central Hospital, Qingdao 266042, China.
Department of Spinal Surgery, Qingdao Central Hospital, Qingdao 266042, China
Biosci Rep. 2019 Feb 1;39(2). doi: 10.1042/BSR20181346. Print 2019 Feb 28.
To identify the association between the interleukin (IL) 6 () rs1800795 (-174 G>C), rs4073 (-251T>A), and matrix metalloproteinase-13 () rs2252070 (-77G>A) gene polymorphisms and knee osteoarthritis (KOA) susceptibility in the Chinese Han population. 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 rs1800795 (-174 G/C), rs4073 (-251A/T), and rs2252070 (-77A/G) loci. The mRNA expression levels of , and in osteoblasts and the protein expression levels of IL-6, IL-8, and MMP-13 in the synovial fluids of KOA patients were analyzed. 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, <0.001). The rs4073 locus dominant and recessive model showed no significant association with KOA risk (>0.05). The dominant and recessive models of the rs2252070 locus showed higher risk for developing KOA (dominant model: adjusted OR = 1.271, 95%CI = 1.095-1.480, =0.001; recessive model: adjusted OR = 1.361 95%CI = 1.151-1.569, <0.001). The G>C mutation in IL-6 rs1800795 and the G>A mutation in 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 rs2252070 locus was associated with up-regulation of MMP-13 expression. The rs4073 (-251T>A) mutation was not associated with KOA susceptibility. The rs1800795 (-174 G>C) and rs2252070 (-77G>A) mutations were associated with KOA susceptibility, increased disease severity, and up-regulation of IL-6 and MMP-13 expression levels.
为了确定白细胞介素（IL）6（rs1800795-174G>C）、rs4073（-251T>A）和基质金属蛋白酶-13（rs2252070-77G>A）基因多态性与中国汉族人群膝骨关节炎（KOA）易感性之间的关系。从 400 例 KOA 患者和 400 例健康对照中提取基因组 DNA。采用 Sanger 测序法确定 rs1800795（-174G>C）、rs4073（-251A/T）和 rs2252070（-77A/G）位点的基因型。分析 KOA 患者成骨细胞中、IL-6、IL-8 和 MMP-13 的 mRNA 表达水平以及 KOA 患者滑膜液中 IL-6、IL-8 和 MMP-13 的蛋白表达水平。发现白细胞介素 6 rs1800795 基因座的隐性模型与 KOA 风险相关（调整后的优势比（OR）=1.657，95%置信区间（CI）=1.396-1.866，<0.001）。rs4073 基因座的显性和隐性模型与 KOA 风险无显著相关性（>0.05）。rs2252070 基因座的显性和隐性模型显示出更高的 KOA 发病风险（显性模型：调整后的 OR=1.271，95%CI=1.095-1.480，=0.001；隐性模型：调整后的 OR=1.361，95%CI=1.151-1.569，<0.001）。白细胞介素 6 rs1800795 的 G>C 突变和 rs2252070 的 G>A 突变与 KOA 疾病严重程度显著相关。白细胞介素 6 rs1800795 基因座的 G>C 突变与 IL-6 表达上调有关。rs2252070 基因座的 G>A 突变与 MMP-13 表达上调有关。rs4073（-251T>A）突变与 KOA 易感性无关。rs1800795（-174G>C）和 rs2252070（-77G>A）突变与 KOA 易感性、疾病严重程度增加以及 IL-6 和 MMP-13 表达水平上调有关。
