缓激肽B2受体基因多态性+9/-9bp对骨关节炎患者血清NO产物水平的影响
Effect of BDKRB2 +9/-9bp polymorphism on the serum NO production in patients with knee osteoarthritis
  
DOI:10.3969/j.issn.1006.7108.2018.01.004
中文关键词:  缓激肽受体B2(BDKRB2)  基因多态性  骨关节炎(OA)
英文关键词:Bradykinin B2 receptor (BDKRB2)  Gene polymorphism  Osteoarthritis (OA)
基金项目:国家自然科学基金资助项目(81301582);中国博士后科学基金面上资助项目(2015M572812)
作者单位
施犇 陈烁∆ 赵建宁* 第二军医大学南京临床医学院 南京总医院骨科江苏 南京 210002 
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中文摘要:
      目的 为研究缓激肽B2受体(BDKRB2)基因多态性+9/-9bp与骨关节炎(OA)患者血清中一氧化氮(NO)产物水平的关系,从而更好的了解OA的发病机制。方法 本研究共招募了156名膝关节骨关节炎患者和58名健康志愿者参与实验。参与研究对象OA患者的BDKRB2基因多态性被测定后按基因型进行分组,在OA患者滑膜组织中通过实时定量聚合酶链反应(qRT-PCR)检测BDKRB2的mRNA产物表达水平,通过NO检测试剂盒检测血清中NO产物水平。结果 我们发现与+9/+9bp基因型组相比,+9/-9bp和-9/-9bp基因型OA患者血清中NO产物水平更高。相关性分析显示BDKRB2 mRNA与NO水平呈显著正相关。与健康对照者相比,OA患者血清中NO产物水平显著升高,并且随着Kellgren-Lawrence(KL)评分增加而增加。多重线性回归分析(MLR)所示(性别和年龄校正后)血清NO产物水平与BDKRB2多态性和KL评分呈正相关,与肥胖呈负相关。结论 本研究提示缓激肽B2受体基因+9/-9bp多态性影响骨关节炎病人中BDKRB2受体基因以及NO产物的表达,其可能作为骨关节炎的一个遗传调制机制在炎症过程中起着关键作用。
英文摘要:
      Objective To investigate the association between the genetic polymorphism of bradykinin B2 receptor (BDKRB2) +9/-9bp and the serum nitric oxide (NO) production, in order to better understand the mechanism of osteoarthritis (OA). Methods This study enrolled 156 subjects with primary knee OA and 58 healthy volunteers. BDKRB2 polymorphisms were genotyped, and the mRNA level of BDKRB2 in synovial tissues of OA patients was measured with quantitative real-time PCR. Serum NO production of OA patients was measured using a NO assay kit. Results OA patients with +9/-9bp and -9/-9bp genotypes had higher NO production in serum. Moreover, positive correlation was found between BDKRB2 levels in synovial tissue and NO production. Comparing with that in health controls, NO production increased more in OA patients, and the increase was associated with increase of Kellgren-Lawrence (KL) grade. Multiple linear regression analysis (after adjusted for gender and age) showed that serum NO level was positively associated with BDKRB2 polymorphism and KL grade, and was negatively associated with obesity. Conclusion BDKRB2 +9/?9bp polymorphism affects the gene expression of BDKRB2 and NO production, suggesting that BDKRB2 +9/?9bp polymorphism may act as a genetic modulator of OA and play an essential role in inflammatory process in OA.
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