骨保护素基因多态性与椎间盘退变的相关性研究

Associations between osteoprotegerin gene polymorphisms and intervertebral disc degeneration

目的探讨骨保护素基因3种常见位点多态性950T/C（rs2073617）、1181G/C（rs2073618）和163A/G（rs3102735）及骨保护素蛋白表达水平与椎间盘退变的相关性。方法选择2013年1月至2014年5月于南华大学附属第一医院就诊的200例椎间盘退变患者作为病例组，同期体检的200例健康志愿者作为对照组。采用PCR-RFLP法检测研究对象骨保护素基因rs2073617、rs2073618和rs3102735位点基因型和单倍型频率分布情况，运用ELISA法检测血清骨保护素水平。采用SPSS22.0统计学软件进行数据分析。结果病例组和对照组骨保护素基因rs2073617多态性的等位基因和基因型频率比较，差异有统计学意义（P＜0.05），携带C等位基因可能会增加椎间盘退变风险[OR=1.79（1.33～2.41），P＜0.001]，但两组rs2073618和rs3102735多态性等位基因和基因型频率差异均无统计学意义（均P＞0.05）。携带骨保护素基因rs2073617多态性3种不同基因型（TT、TC和CC）椎间盘退变患者的血清骨保护素水平均明显高于健康对照组（均P＜0.05）；而携带rs3102735和rs2073618多态性不同基因型患者的血清骨保护素水平与对照组比较，差异均无统计学意义（均P＞0.05）。单倍型分析结果显示，骨保护素基因T-G-A单倍型可能是椎间盘退变的保护性因素（OR=0.62，95%CI=0.41～0.94，P=0.020），而C-G-G单倍型可能为椎间盘退变的危险因素（OR=2.24，95%CI=1.09～4.60，P=0.020）。Logistic回归分析结果表明，低血清骨保护素水平与椎间盘退变发生风险呈正相关，而T-C-A、T-G-A和T-G-G单倍型与椎间盘退变发生风险呈负相关（均P＜0.05）。结论骨保护素基因rs2073617多态性可能与椎间盘退变有关，但rs2073618和rs3102735多态性可能不是增加椎间盘退变易感性的主要危险因素；骨保护素基因T-C-A、T-G-A和T-G-G单倍型可能是椎间盘退变的保护性因素，低血清骨保护素水平则可能是椎间盘退变的危险因素。

Objective To investigate the correlations of osteoprotegerin(OPG)-950T/C(rs2073617),-1181G/C(rs2073618),-163A/G(rs3102735)polymorphisms,serum OPG levels,and intervertebral disc degeneration(IDD).Methods A total of200IDD patients treated in the First Affiliated Hospital of Nanhua University from January2013to May2014were recruited as the case group,and200healthy volunteers were selected as the control group simultaneously.Genotype and haplotype frequency distributions of OPG polymorphisms were analyzed by PCR-RFLP assay,serum OPG levels were measured by ELISA.SPSS22.0software was used to analyze.Results Genotype and allele frequencies of OPG rs2073617polymorphism were significantly higher in case group compared to those in control group(P<0.05).The C allele carriers showed a higher risk of IDD than T allele carriers[OR=1.79(1.33-2.41),P<0.001].The genotype and allele frequencies of two other gene polymorphisms,rs2073618and rs3102735,showed no statistical differences between patients and controls(P>0.05).Furthermore,OPG serum levels in case group with TT,TC and CC genotypes in OPG rs2073617polymorphism were markedly higher than those in control group(P<0.05);while there were no statistical differences of OPG serum levels between controls and IDD patients who carried different genotypes in OPG rs2073618and rs3102735polymorphisms.The haplotype analysis showed that T-G-A haplotype associated with protection against IDD(OR=0.62,95%CI=0.41-0.94,P=0.02),while C-G-G haplotype associated with elevated susceptibility to IDD(OR=2.24,95%CI=1.09-4.60,P=0.02).Logistic-regression analysis indicated that low serum levels of OPG positively correlated with IDD risk,while the T-C-A,T-G-A and T-G-G haplotypes negatively correlated with IDD risk(P<0.05).Conclusions OPG rs2073617polymorphism is strongly connected with increased risk of IDD,but rs2073618and rs3102735might not be major risks of increasing IDD susceptibility.Low OPG serum level maybe increases IDD risk;By contrast,T-C-A,T-G-A and T-G-G haplotypes are protective factors for IDD probably.