正常-脑瘫病证双生子印记基因筛选——功能分析与随机验证研究  

Screening of Imprinted Genes in Normal-Cerebral Palsy Twins:Functional Analysis and Randomized Validation Study

作　　者：朱海燕 张春江 黄丽莉 董小丽[2] 尹巧芝[3] 张天娥[1] Zhu Haiyan;Zhang Chunjiang;Huang Lili;Dong Xiaoli;Yin Qiaozhi;Zhang Tiane(School of Basic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu,611137,China;Chengdu First People’s Hospital,Chengdu,610095,China;The Second Clinical Medical College of Chengdu University of Traditional Chinese Medicine,Chengdu,610042,China)

机构地区：[1]成都中医药大学基础医学院,四川成都611137 [2]成都市第一人民医院,四川成都610095 [3]成都中医药大学第二临床医学院,四川成都610042

出　　处：《成都中医药大学学报》2023年第5期28-33,42,共7页Journal of Chengdu University of Traditional Chinese Medicine

基　　金：四川省科技计划科研院所科技成果转化项目(2020JDZH0018);成都中医药大学“双一流”建设项目(XSGG2018002)。

摘　　要：目的:探索脑瘫印记基因表达差异,进行差异基因验证,明晰印记基因与脑瘫的因果关系,为脑瘫的早期生物学诊断提供候选靶标。方法:提取正常-脑瘫双生对mRNA,行全基因组表达谱芯片检测,筛选其中的差异印记基因,随机采集同龄脑瘫患儿、发育落后儿、正常儿外周血提取mRNA,利用RT-qPCR对筛选出的部分差异印记基因进行验证。结果:获取15个差异印记基因,包括GPR1、SPON2、SLC22A18、FLJ13081、COPG2、ZIC1、TFPI2、SLC4A2、IGF2R、HSPA6、GATA3、FAM50B、EGFL7、BRP44L、APBA1;RT-qPCR结果显示,与正常组比较COPG2、HSPA6、BRP44L、SLC22A18基因在脑瘫组和发育落后组相对表达量降低,其中脑瘫组和发育落后组COPG2相对表达量降低程度不同(P<0.01,P>0.05),脑瘫组、发育落后组HSPA6相对表达量降低(P<0.01,P<0.05),脑瘫组、发育落后组SLC22A18、BRP44L相对表达量降低(P<0.01),脑瘫组FAM50B相对表达量降低(P<0.05)。结论:脑瘫表现的生长发育迟缓、语言障碍及智力障碍可能与COPG2、FAM50B和HSPA6表达下调有关,发育落后患儿和脑瘫患儿低体重、发育异常可能与SLC22A18与BRP44L表达下调有关,GATA3与IGF2R可能与胎盘滋养层细胞功能异常有关。据此表达差异,印记基因SLC22A18、BRP44L、COPG2、FAM50B和HSPA6可作为脑瘫早期诊断的候选基因,以期为脑瘫生物学早期诊断提供依据。Objective:To explore the differential expression of imprinted genes in cerebral palsy,and to verify them.So as to clarify the causal relationship between imprinted genes and Cerebral palsy,and provides candidate targets for the early biological diagnosis of cerebral palsy.Methods:The Normal-cerebral palsy twins were extracted to perform whole genome expression profile chip detection of mRNA,screened for differential imprinted genes.While randomly collecting peripheral blood from children with Cerebral palsy,developing backwards and normal children of the same age to extract mRNA,and verified some of the differential imprinted genes screened by real-time quantification(RT-qPCR).Results:Screened out 15 differentially imprinted genes,including GPR1、SPON2、SLC22A18、FLJ13081、COPG2、ZIC1、TFPI2、SLC4A2、IGF2R、HSPA6、GATA3、FAM50B、EGFL7、BRP44L、APBA1.RT-qPCR results show that,compared with normal group,the expression of COPG2、HSPA6、BRP44L and SLC22A18 in the Cerebral palsy group and the developmental backward group were decreased.Among which the relative expression of COPG2 in the Cerebral palsy group and the developmental backward group decreased(P<0.01,P>0.05),the content of HSPA6 in the Cerebral palsy group and the developmental backward group was reduced(P<0.01,P<0.05),and the Cerebral palsy group and the developmental backward group SLC22A18.The relative expression of BRP44L was reduced(P<0.01),and the relative expression of FAM50B in the Cerebral palsy group was reduced(P<0.05).Conclusion:Growth retardation,language impairment,and intellectual disability of Cerebral palsy are associated with downregulation of COPG2,FAM50B,and HSPA6,low body weight and developmental abnormalities in children with developmental delay and cerebral palsy are associated with downregulation of SLC22A18 and BRP44L,and GATA3 and IGF2R may be related to abnormal trophoblast cell function.Therefore,SLC22A18,BRP44L,COPG2,FAM50B and HSPA6 can be used as candidate targets for the early diagnosis of Cerebral palsy in ord

关 键 词：脑性瘫痪 同卵双生子 印记基因 差异表达 早期诊断 

分 类 号：R742.3[医药卫生—神经病学与精神病学] R392.2[医药卫生—临床医学]