两种基因多态性与退行性腰椎管狭窄症的关联性分析

Study on the Association between Two Gene Polymorphismand Degenerative Lumbar Spinal Stenosis

目的:分析腰椎管狭窄症(Lumbar Spinal Stenosis,LSS)高发体质类型肝肾亏虚型与COL11A1、HBOX4位点多态性的相关性。方法:根据诊断和排除标准,随机抽取甘肃省中医院脊柱骨二科2016年6月至2018年6月门诊和住院治疗的退行性腰椎管狭窄症患者80例为病例组,以来自甘肃省中医院脊柱骨二科门诊的80例非腰椎退行性疾患患者为对照组,与病例组匹配,其中肝肾亏虚型35例,非肝肾亏虚型45例。抽取外周血2 mL作为检测样本,提取DNA,对PCR产物进行DNA测序,检测COL11A1、HBOX4基因的2个位点(即rs1676486、rs520540位点),进行统计学分析。结果:COL11A1的rs1676486与等位基因频率病例组高于对照组(P<0.05),可能是导致腰椎管狭窄症的危险因素之一;对照组HBOX4的rs520540位点CT、TT、CC基因表达病例组低于对照组(P<0.05),可能是预防腰椎管狭窄症的因素之一。结论:COL11A1基因与6p21.3C/G位点多态性与腰椎管狭窄症之间存在一定关联性。选取COL11A1的一个SNP位点rs14637185,发现腰椎管狭窄患者的COL11A1基因型频率和等位基因型频率均高于非腰椎疾患的患者,但从中继续深入研究发现COL11A1、HBOX4基因的多态性与肝肾亏虚型腰椎管狭窄症患者存在一定相关性;HBOX4位于17q21的rs520540位点CT、TT、CC上调能够降低腰椎管狭窄症的发病率,将为治疗腰椎退行性病变提供新的治疗靶点。

Objective:To investigate the correlation between lumbar spinal stenosis and high case type of liver and kidney deficiency and the polymorphism of COL11 A1 and HBOX4.Methods:Research objects were selected according to the diagnosis and exclusion criteria.80 patients with degenerative lumbar spinal stenosis were randomly selected as the study group from June 2016 to June 2018 in hospital.80 patients with non-lumbar degenerative diseases from hospital were taken as the control group and matched with case group,and there were 35 cases of liver and kidney deficiency type and 45 cases of liver and kidney deficiency type.2 mL peripheral blood was extracted as the detection sample.DNA was extracted.DNA sequencing was performed on PCR products,and two loci of COL11 A1 and HBOX4 genes,namely rs1676486 and rs520540,were detected for statistical analysis.Results:rs1676486 and allele frequency of COL11 A1 in the case group were higher than those in the control group(P<0.05),which may be one of the risk factors for lumbar spinal stenosis.The expression of CT,TT and CC genes at rs520540 of HBOX4 was lower in the experimental group than in the control group (P<0.05),which may be one of the factors for the prevention of lumbar spinal stenosis.Conclusion:There is a certain correlation between COL11 A1 gene and 6 P21.3 C/G polymorphism and lumbar spinal stenosis.The SNP locus of COL11 A1,rs14637185 is selected,and it is found that the frequency of COL11 A1 genotype and allelic genotype in patients with lumbar spinal stenosis are higher than that in those without lumbar diseases.However,further studies find that polymorphisms of COL11 A1 and HBOX4 genes are correlated with patients with lumbar spinal stenosis with liver-kidney deficiency.Up-regulation of CT,TT and CC at rs520540 of HBOX4 at 17 q21 can reduce the incidence of lumbar spinal stenosis,which will provide a new therapeutic target for the treatment of lumbar degenerative diseases.