缓激肽B2受体基因多态性对膝关节骨关节炎易感性的影响  

The effect of BDKRB2 gene polymorphism on the risk of knee osteoarthritis

作　　者：陈烁[1] 周利武[1] 张雷[1] 赵云龙[2] 杨超[2] 赵建宁[1] 

机构地区：[1]南京军区南京总医院骨科,江苏南京210002 [2]南京大学医学院临床学院骨科,江苏南京210000

出　　处：《中国骨质疏松杂志》2016年第2期139-144,共6页Chinese Journal of Osteoporosis

基　　金：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);江苏省博士后科研资助项目(1402003B);江苏省临床医学科技专项资助项目(BL2012002);全军医学科技青年培育项目(13QNP044)

摘　　要：目的明确BDKRB2基因多态性与OA易感性的相关性,并检测OA患者基因多态性对滑膜组织中BDKRB2表达的影响。方法共有278名膝关节骨关节炎患者和291名健康志愿者参与实验。测定实验对象的BDKRB2基因多态性,在OA患者滑膜组织中通过RT-PCR和Western Blot检测BDKRB2的m RNA和蛋白水平。结果 OA组和对照组中＋9/-9 bp多态性的基因型分布和等位基因频率差异明显。-9/-9 bp多态性和＋9/＋9 bp相比,与OA的罹患风险和严重程度存在明显相关性（OR=2.35,95%CI：1.409~3.937,P〈0.001）。-9 bp等位基因的表达,与OA的Kellgren-Lawrence分型相关（OR=1.545,,P=0.011）。另外,＋9/-9 bp多态性显著影响OA患者滑膜组织中BDKRB2的m RNA和蛋白表达。＋9/-9和-9/-9基因型在滑膜组织中BDKRB2的表达水平显著升高,同时KL4型OA患者平均BDKRB2 m RNA和蛋白水平明显高于其他对象（2.502±1.319 vs.1.471±1.002和1.895±1.174,P〈0.001）。结论本研究提示BDKRB2基因＋9/-9bp多态性可能成为OA易感性和严重性筛查的分子标记。Objective To explore the relationship between bradykinin B2 receptor （BDKRB2） polymorphism and osteoarthritis （ OA）, and to examine the effect of gone polymorphisms on BDKRB2 expression in synovial tissue in OA patients. Methods Two hundred and seventy-eight knee OA patients and 291 healthy volunteers were enrolled. BDKRB2 gone polymorphism was genotyped. The mRNA and protein levels of BDKRB2 in synovial tissues from OA patients were measured using quantitative real- time PCR and Western blotting analysis. Results The genotype distribution and allele frequency of ＋ 9/- 9 bp polymorphism was significantly different between OA and control subjects. The -9/-9 polymorphism was significantly associated with the increased risk and the radiographic severity of knee OA comparing to the ＋ 9/＋ 9 genotype （ OR = 2.35, 95% CI： 1. 409 - 3. 937, P 〈 0. 001 ）. The presence of - 9 bp was associated with higher KeUgren-Lawrence grade of OA （ OR = 1. 545, P = 0. 011 ）. Moreover, the ＋ 9/-9bp polymorphism significantly affected the mRNA and protein expression levels of BDKRB2 in synovial tissues in OA subjects. Subjects with ＋ 9/- 9 and - 9/- 9 genotypes had higher BDKRB2 expression levels in synovial tissue. The mean BDKRB2 mRNA and protein levels in KL grade 40A patients were significantly higher than those in other subjects. Conclusion Our findings suggest that the ＋ 9/-9bp polymorphism of BDKRB2 gone may be used as a molecular marker for the susceptibility and severity of OA.

关 键 词：缓激肽受体B2(BDKRB2) 骨关节炎(OA) 基因多态性 

分 类 号：R684.3[医药卫生—骨科学]