椎间盘退行性变与HTRA1和HAPLN1基因多态性的相关性  

Association of HTRA1 and HAPLN1 gene polymorphism with intervertebral disc degeneration

作　　者：杨金丰 马三辉 Yang Jinfeng;Ma Sanhui(Department of Orthopedics,People’s Hospital of Dingzhou,Dingzhou 073000,Hebei Province,China)

机构地区：[1]定州市人民医院骨科,河北省定州市073000

出　　处：《中国组织工程研究》2020年第32期5128-5132,共5页Chinese Journal of Tissue Engineering Research

基　　金：河北省卫生厅科研基金项目(20181772),项目负责人:杨金丰。

摘　　要：背景:研究发现,HTRA1基因启动子区域的单核苷酸多态性基因型与椎间盘退变相关,而HAPLN1基因与椎间盘退变引起的骨关节炎相关。目的:探讨分泌型丝氨酸蛋白酶HTRA1和骨细胞外基质的关键组分HAPLN1变异在椎间盘退变发病机制中的作用。方法:选择2015年4月至2018年12月在定州市人民医院接受体检的498名绝经后女性受试者,利用Taq ManPCR方法检测受试者HTRA1基因启动子rs11200638单核苷酸多态性和HAPLN1基因5’侧翼rs975563、内含子1rs10942332、内含子2rs179851和内含子4rs4703570的单核苷酸多态性,分析HTRA1和HAPLN1基因多态性与椎间盘退变影像学特征之间的相关性。试验已通过定州市人民医院伦理道德委员会批准。结果与结论:①在498名受试者HTRA1基因rs11200638单核苷酸多态性中,178名为GG纯合子,222名为GA杂合子,98名为AA纯合子,将具有至少一个G等位基因(GG+GA,n=400)和没有G等位基因(AA,n=98)受试者间的椎间盘退变参数进行比较;②在HTRA1基因rs11200638单核苷酸多态性中,GG+GA等位基因组的椎间隙狭窄评分低于AA等位基因组(P<0.001);随着椎间隙狭窄评分的升高,受试者中AA等位基因型发生风险增高(P≤0.001);③在498名受试者HAPLN1基因单核苷酸多态性中,137名为TT纯合子,230名为CT杂合子,131名为CC纯合子,将CC+TT等位基因(n=361)、TT等位基因(n=137)的椎间盘退变参数进行比较;④在HAPLN1基因中,仅rs179851单核苷酸多态性的CC+TT等位基因组与TT等位基因组骨赘形成、椎间隙狭窄存在显著差异(P<0.01);⑤在HAPLN1基因rs179851单核苷酸多态性中,椎间隙狭窄≥6分受试者的TT等位基因型发生风险显著增高(P<0.05);随着骨赘形成评分的升高,受试者TT等位基因TT等位基因型发生风险显著增高(P<0.001);⑥结果表明,HTRA1和HAPLN1特定基因位点的遗传变异与椎间盘退变相关。BACKGROUND:Studies have found that single nucleotide polymorphism genotypes in the HTRA1 gene promoter region are associated with intervertebral disc degeneration,while HAPLN1 is associated with osteoarthritis caused by intervertebral disc degeneration.OBJECTIVE:To explore the role of human secretory serine protease HTRA1 and the key group of extracellular matrix HAPLN1 in the pathogenesis of intervertebral disc degeneration.METHODS:This study included 498 postmenopausal female subjects who underwent a physical examination at Dingzhou People’s Hospital from April 2015 to December 2018.TaqMan PCR was used to detect HTRA1 gene promoter rs11200638 single nucleotide polymorphism and HAPLN1 gene 5’flanking rs975563,intron 1 rs10942332,intron 2 rs179851 and intron 4 rs4703570 single nucleotide polymorphism in 498 postmenopausal Chinese women.The correlation between the HTRA1 orHAPLN1 gene polymorphisms and the radiographic features of spinal disc degeneration was analyzed.The trial has been approved by the Ethics Committee of Dingzhou People’s Hospital.RESULTS AND CONCLUSION:Among the 498 subjects with the HTRA1 gene rs11200638 single nucleotide polymorphism,178 were GG homozygotes,222 were GA heterozygotes,and 98 were AA homozygotes.We compared the parameters of intervertebral disc degeneration in subjects with at least one G allele(GG+GA,n=400)and without G allele(AA,n=98).In HTRA1 gene rs11200638 single nucleotide polymorphism,the score on intervertebral space stenosis in the subjects with GG+GA allele genome was lower than that in the subjects with AA allele(P<0.001).With the increase of the score on intervertebral space stenosis,the proportion of the subjects with AA alleles increased(P≤0.001).Among the 498 subjects with single nucleotide polymorphisms of the HAPLN1 gene,137 were homozygous for TT,230 were heterozygous for CT,and 131 were homozygous for CC.Intervertebral disc degeneration parameters of CC+TT allele(n=361)and TT allele(n=137)were compared.In the HAPLN1 gene,there was a significant differenc

关 键 词：单核苷酸多态性 HTRA1基因 HAPLN1基因 椎间盘退变 遗传变异 等位基因 骨赘形成 椎间隙狭窄 

分 类 号：R459.9[医药卫生—治疗学] R681.5[医药卫生—临床医学]