基质金属蛋白酶3基因多态性与膝骨性关节炎的遗传易感性

Relationship between matrix metalloproteinase-3 gene polymorphism and genetic susceptibility to knee osteoarthritis

背景:虽然近年来对膝骨性关节炎的起因、发展及防治取得了很大进展,但是目前其具体病因及发病机制仍不明确。在致病因素中,遗传因素占40%-60%,与膝骨性关节炎的发病有着紧密的联系。目的:探索基质金属蛋白酶3基因多态性与中国北方汉族人群中膝骨性关节炎患者发病的关联性。方法:选择2018年10月至2020年10月在内蒙古医科大学附属医院就诊的膝骨性关节炎患者100例与健康体检者197名,均为汉族男性,采用试剂盒提取血液全基因组DNA后,采用Sequenom MassARRAY技术平台对基质金属蛋白酶3基因的8个单核苷酸多态性位点(rs639752、rs650108、rs520540、rs646910、rs602128、rs679620、rs678815、rs522616)进行单核苷酸多态性分型。采用无条件Logistic回归分析计算单核苷酸多态性在5种遗传模型下(共显性、显性、隐性、超显性和加性模型)与膝骨性关节炎的关联性。结果与结论:(1)经Pearson卡方检验可知,所有位点在等位基因模型下与膝骨性关节炎的患病风险无相关性;(2)通过关联分析发现,基质金属蛋白酶3基因4个位点(rs639752、rs520540、rs602128和rs6796204)的多态性在显性和超显性模型下与膝骨性关节炎存在统计学上的相关性;(3)结果表明,基质金属蛋白酶3基因位点rs639752、rs520540、rs602128和rs679620会增加中国北方汉族人群男性膝骨性关节炎的发病率,但该结果需要在更大的样本中行进一步验证。

BACKGROUND:Although great progress has been made in the etiology,development and treatment of knee osteoarthritis in recent years,its specific etiology and pathogenesis are still unclear.Among the pathogenic factors of knee osteoarthritis,genetic factors account for about 40%-60%,which are closely related to the incidence of knee osteoarthritis.OBJECTIVE:To investigate the relationship between matrix metalloproteinase-3 gene polymorphism and onset of knee osteoarthritis in Han population in north China.METHODS:We recruited 100 male patients with knee osteoarthritis and 197 healthy men admitted at the Affiliated Hospital of Inner Mongolia Medical University between October 2018 and October 2020.All the subjects were from the Han group.We used commercial kits to extract the blood genomic DNAs.Eight single nucleotide polymorphisms of matrix metalloproteinase-3 gene,including rs639752,rs650108,rs520540,rs646910,rs602128,rs679620,rs678815,and rs522616,were genotyped by using the Sequenom MassARRAY RS1000 platform.Unconditional Logistic regression analysis was used to calculate the correlation between single nucleotide polymorphisms and knee osteoarthritis under five genetic models(codominant,dominant,recessive,overdominant and additive models).RESULTS AND CONCLUSION:(1)In the Pearson chi-square test,all loci had no correlation with the risk of knee osteoarthritis under the allelic model.(2)Through the association analysis,we identified that four single nucleotide polymorphisms(rs639752,rs520540,rs602128,and rs679620)in the matrix metalloproteinase-3 gene in the dominant and over-dominant models were associated with the increased risk of knee osteoarthritis.(3)Our study preliminarily revealed that four single nucleotide polymorphisms(rs639752,rs520540,rs602128,and rs679620)in the matrix metalloproteinase-3 gene can increase the incidence of knee osteoarthritis in men of Han ethnics in north China.However,the results we identified here need to be confirmed in further large-scale studies.