酰基辅酶A:胆固醇酰基转移酶1在骨关节炎中的表达差异及其遗传相关性分析  

Differential expression of Acyl⁃CoA:cholesterol acyltransferase 1(ACAT1)in osteoarthritis and its genetic correlation analysis

作　　者：黄维 卢炜[1] 夏小鹏[1] 李南 陈颖 Huang Wei;Lu Wei;Xia Xiaopeng;Li Nan;Chen Ying(Nantong Hospital of Traditional Chinese Medicine,Nantong 226001,China)

机构地区：[1]南通市中医院,江苏南通226001 [2]南通大学医学院组织学与胚胎学系

出　　处：《海军医学杂志》2024年第6期612-617,共6页Journal of Navy Medicine

摘　　要：目的 研究酰基辅酶A:胆固醇酰基转移酶1(ACAT1)在骨关节炎(OA)中的表达差异及其遗传相关性。方法通过基因表达综合(GEO)数据库分析ACAT1在OA患者滑膜组织和OA小鼠滑膜组织中表达情况。构建小鼠OA模型通过苏木精-伊红(HE)染色验证OA模型构建情况,并通过RT-PCR检测ACAT1的表达。通过全基因组遗传相关性分析剖析ACAT1高度协同作用基因。结果 ACAT1在OA患者滑膜组织和OA小鼠滑膜组织中表达下调;ACAT1在不同品系BXD和BXH RI小鼠软骨组织中的表达变化呈线性变化趋势,提示ACAT1基因表达变化属于典型数量遗传性状,受多因素调控。约500个基因与ACAT1基因遗传相关性呈高度相关(P<0.05),其中包括一系列与细胞膜的结构、细胞间的连接与信号通路、基因转录调控和蛋白质稳定性等相关的基因。结论 ACAT1可以作为治疗OA的新靶点。Objective To investigate the differential expression of Acyl-CoA:cholesterol acyltransferase 1(ACAT1)in osteoarthritis(OA)and its genetic correlation.Methods The expression of ACAT1 in synovial tissues of OA patients and OA mice was analyzed by using GEO database.The OA model was verified by haematoxylin-eosin(H-E)staining.The expression of ACAT1 was detected by RT-PCR.The highly synergistic genes of ACAT1 were analyzed by genome-wide genetic correlation analysis.Results The expression of ACAT1 was down-regulated in synovial tissues of OA patients and OA mice.The changes of ACAT1 expression in cartilage tissues of different strains of BXD and BXH RI mice showed a linear trend,indicating that the expression of ACAT1 gene presented with a typical quantitative genetic trait and was regulated by multiple factors.About 500 genes were highly correlated with ACAT1(P<0.05),including genes related to cell membrane structure,cell-to-cell connectivity and signaling pathways,gene transcription regulation,and protein stability.Conclusion ACAT1 may be a new target for the treatment of OA.

关 键 词：骨关节炎 胆固醇 酰基辅酶A:胆固醇酰基转移酶 遗传相关性分析 

分 类 号：R394.3[医药卫生—医学遗传学]