摘要
目的探讨带有血小板凝血酶敏感蛋白样模体的解整链蛋白金属蛋白酶5(ADAMTS-5)基因单核苷酸多态性(SNP)与膝骨关节炎的关联性。方法连续收集洛阳正骨医院188例膝骨关节炎患者作为病例组,对照组收集排除疾病诊断的100人。应用基因组变异服务器(GVS)网站选择ADAMTS-5基因共计15个SNP位点,采用基质辅助激光解析飞行时间质谱分析技术(MALDI-TOF-MS)进行SNP分型,先行哈迪温伯格(HW)平衡检测,对符合HW平衡的SNP位点等位基因进行卡方检验及单体型分析,对基因型进行logistic回归分析。结果病例组rs2249350位点C等位基因显著多于对照组[比值比(OR)=1.176,95%置信区间(CI)(1.025,1.351),P=0.016],A等位基因显著少于对照组[OR=0.761,95%CI(0.612,0.947),P=0.016];rs2249350位点AA基因型[OR=0.288,95%CI(0.124,0.669),P=0.004]及隐性基因模型[OR=0.348,95%CI(0.162,0.749),P=0.007]均与膝关节骨关节炎负相关;rs229054、rs2249350两位点存在连锁不平衡,构成GC、GA、AC共3个单体型区块,其中病例组单体型GC显著多于对照组[OR=1.259,95%CI(1.032,1.537),P=0.019],而GA则显著少于对照组[OR=0.763,95%CI(0.614,0.949),P=0.017]。结论ADAMTS-5基因rs2249350位点C等位基因可能是膝关节骨关节炎的致病性因素,A等位基因则可能是保护性因素;rs2249350位点AA基因型可能是膝关节骨关节炎的保护性基因型,降低患病风险,且A等位基因可能为隐性基因,隐性遗传;rs229054、rs2249350位点GC单体型可能是膝关节骨关节炎的致病性因素,而GA单体型则可能是保护性因素。该位点等位基因、基因型及单体型与膝关节骨关节炎的关系仍需进一步深入研究和验证。
Objective To investigate the relationship between knee osteoarthritis(KOA)susceptibility and single nucleotides polymorphism(SNP)of a disinterring and metalloproteinase with thrombospondin motifs 5(ADAMTS-5)gene.Methods A total of 188 patients with KOA from Luoyang Orthopedic Hospital were collected as the case group,and 100 patients in the control group were excluded from disease diagnosis.Fifteen SNP of ADAMTS-5 genes were chosen by Genome Variation Server(GVS)online gene database.SNP typing was identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The Hardy-Weinberg equilibrium test was carried out first,chi-square test and Haplotype analysis were carried out on the allele of SNP locus in accordance with the Hardy-Weinberg balance,and then logistic regression analysis was carried out on the genotype.Results The C allele of rs2249350 locus in the case group was significantly higher than that in the control group[odds ratios(OR)=1.176,95%confidence interval(CI)(1.025,1.351),P=0.0016],the A allele was significantly lower than that in the control group[OR=0.761,95%CI(0.612,0.947),P=0.016].AA genotype[OR=0.288,95%CI(0.124,0.669),P=0.004]and recessive gene model[OR=0.348,95%CI(0.162,0.749),P=0.007]at rs2249350 locus were negatively correlated with osteoarthritis of the knee joint.There was linkage disequilibrium between the two sites of rs229054 and rs2249350,which formed three single haplotype blocks of GC,GA,and AC.The haplotype GC in the case group was significantly higher than that in the control group[OR=1.259,95%CI(1.032,1.537),P=0.019],while the GA in the case group was markedly lower than that in the control group[OR=0.763,95%CI(0.614,0.949),P=0.017].Conclusions The C allele of rs2249350 site of ADAMTS-5 gene may be the pathogenic factor of knee osteoarthritis,while the A allele may be the protective factor.AA genotype at rs2249350 site may be a protective genotype of osteoarthritis of the knee joint,which reduces the risk of disease,and A allele may be a re
作者
高山
孙乾坤
王敬威
胡梅
郭艳幸
Gao Shan;Sun Qiankun;Wang Jingwei;Hu Mei;Guo Yanxing(Neck and waist pain Department of Weifang Traditional Chinese Medicine Hospital, Weifang 261041, China;Emergency Department of Luoyang No. 1 Traditional Chinese Medicine Hospital, Luoyang 471000, China;Luoyang Orthopedic Hospital(Henan province Orthopedic Hospital), Luoyang 471000, China;Hunan University of Traditional Chinese Medicine, Changsha 410208, China)
出处
《中华关节外科杂志（电子版）》
CAS
CSCD
2020年第4期454-460,共7页
Chinese Journal of Joint Surgery(Electronic Edition)
基金
国家中医药管理局“平乐郭氏正骨流派传承工作室”建设项目([2012]228)
河南省科技厅“国家非物质文化遗产—平乐郭氏正骨术的系统研究与开发”项目(112102310008)
河南省中医药管理局“河南省中医临床学科领军人才培育计划”项目(HNZYLJ20131009)。
