基质金属蛋白酶-3和维生素D受体基因多态性与职业危险因素在腰椎间盘退变发生中的协同作用

Synergistic interaction between MMP-3,VDR gene polymorphisms and occupational risk factors on lumbar disc degeneration

目的探索基质金属蛋白酶-3（MMP-3）、维生素D受体（VDR）的基因多态性与职业危险因素在腰椎间盘退变发生中的协同作用。方法采用病例对照研究方法，对178名腰椎间盘退变患者及284名腰椎功能正常者进行职业危险因素问卷调查；同时应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测MMP-3与VDR的基因多态性，并应用相加模型分析基因多态性与职业危险因素在腰椎间盘退变中的协同作用。结果非条件logistic回归分析显示，重度弯腰扭腰、全身振动及重体力负荷的OR值分别为4．06，8．96，5．46（P〈0．05）；含有MMP-3突变等位基因5A的6A5A／SA5A基因型及含有VDR-Apa突变等位基因A的AA／Aa基因型在病例组中的分布明显高于对照组，其0R值分别为1．96与1．70（P〈0．05）；相加模型分析显示，MMP-3的突变等位基因5A与全身振动、弯腰扭腰之间，以及VDR—Apa的突变等位基因A与弯腰扭腰之间存在协同作用（SI分别为13．27，2．91，2．35，P〈0．05）。结论携带MMP-3的突变等位基因5A或VDR-Apa的突变等位基因A，同时暴露于职业危险因素全身振动或弯腰扭腰，可能增加发生腰椎间盘退变的危险性。

Objective To explore the synergistic interaction between MMP-3,VDR gene polymorphisms and occupational risk factors on lumbar disc degeneration. Methods A case-control study including 178 cases of lumbar disc degeneration and 284 controls was carried out through questionnaire and polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technology. Additive model was used to analyze the synergistic interaction between gene polymorphisms and occupational risk factors. Results The non-conditional logistic regression analysis showed that bending/twisting, whole-body vibration, heavy physical workload, alleles 5A of MMP-3 （6A5A/5A5A） and A of VDR-Apa （AA/Aa） were significantly associated with lumbar disc degeneration（OR=4.06,8.96,5.46,1.96 and 1.70, respectively, P〈0.05）. There were synergistic in- teractions between the mutation genotype 5A of MMP-3 and whole-body vibration exposure, between the muta- tion genotype 5A of MMP-3 and bending/twisting, and between the mutation genotype A of VDR-Apa and whole-body vibration exposure （SI：13.27,2.91 and 2.35 respectively, P〈0.05）. Conclusion People with the mutation genotypes 5A of MMP-3 and/or A of VDR-Apa may have the increased risk of developing lumbar disc degeneration if they are exposed to whole-body vibration and/or bending/twisting.