目的系统评价CDKAL1基因rs7756992位点A>G多态性与2型糖尿病(T2DM)易感性的关系。方法制定原始文献的纳入、排除标准及检索策略,通过检索学术期刊全文数据库(CNKI)、万方数据库及EMBASE、PubMed、ScienceDirect等数据库,收集有关CDK...目的系统评价CDKAL1基因rs7756992位点A>G多态性与2型糖尿病(T2DM)易感性的关系。方法制定原始文献的纳入、排除标准及检索策略,通过检索学术期刊全文数据库(CNKI)、万方数据库及EMBASE、PubMed、ScienceDirect等数据库,收集有关CDKAL1基因rs7756992位点A>G多态性与T2DM易感性的病例对照研究,以病例组与对照组CDKAL1基因rs7756992位点各种基因模型的比值比(OR)及其95%置信区间(CI)为效应指标进行meta分析,并根据研究人群种族不同进行亚组分析。结果本研究共纳入15篇文献,T2DM组和对照组病例数分别为24 315例和35 132例。Meta分析显示,CDKAL1基因rs7756992位点A>G多态性与T2DM易感性有关联[等位基因模式(G vs A):OR=1.171,95%CI1.122~1.223,P<0.001;共显性模式(GG vs AA):OR=1.380,95%CI1.258~1.515,P<0.001;共显性模式(AG vs AA):OR=1.131,95%CI 1.089~1.176,P<0.001;显性模式(AG+GG vs AA):OR=1.168,95%CI 1.101~1.240,P<0.001;隐性模式(GG vs AA+AG):OR=1.343,95%CI 1.282~1.405,P<0.001]。亚组分析显示,亚洲人群和白种人群中携带CDKAL1基因rs7756992位点G等位基因的人群发生T2DM的风险增加(P<0.05);而非洲人群中携带CDKAL1基因rs7756992位点G等位基因与A等位基因的人群发生T2DM风险的差异无统计学意义。结论在亚洲人群及白种人群中CDKAL1基因rs7756992位点A>G等位基因的突变可能是T2DM发病的危险因素之一。展开更多
AIM:To evaluate the expression status of S-phase kinase-associated protein 2(Skp2)/cyclin-dependent kinases regulatory subunit 1(Cks1)and p27kip1,and assess the prognostic significance of Skp2/Cks1 expression with p27...AIM:To evaluate the expression status of S-phase kinase-associated protein 2(Skp2)/cyclin-dependent kinases regulatory subunit 1(Cks1)and p27kip1,and assess the prognostic significance of Skp2/Cks1 expression with p27kip1in patients with extrahepatic cholangiocarcinoma.METHODS:Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December1994 to March 2008 were enrolled.Immunohistochemical staining for Skp2,Cks1,p27kip1,and Ki67,along with other relevant molecular biologic experiments,were performed.RESULTS:By Cox regression analyses,advanced age(>65 years),advanced AJCC tumor stage,poorly differentiated histology,and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic cholangiocarcinoma.Exogenous epidermal growth factor(EGF,especially 0.1-10 ng/mL)significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27kip1in SNU-1196,SNU-1079,and SNU-245 cells.The protein levels of Skp2/Cks1(from nuclear lysates)and p27kip1(from cytosolic lysate)were also significantly increased in these cells.There were significant reductions in the protein levels of Skp2/Cks1and p27kip1(from nuclear lysate)after the treatment of LY294002.By chromatin immunoprecipitation assay,we found that E2F1 transcription factor directly binds to the promoter site of Skp2.CONCLUSION:Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic cholangiocarcinoma.EGF upregulates the mRNA and protein levels of Skp2/Cks1and p27kip1via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter.展开更多
文摘目的系统评价CDKAL1基因rs7756992位点A>G多态性与2型糖尿病(T2DM)易感性的关系。方法制定原始文献的纳入、排除标准及检索策略,通过检索学术期刊全文数据库(CNKI)、万方数据库及EMBASE、PubMed、ScienceDirect等数据库,收集有关CDKAL1基因rs7756992位点A>G多态性与T2DM易感性的病例对照研究,以病例组与对照组CDKAL1基因rs7756992位点各种基因模型的比值比(OR)及其95%置信区间(CI)为效应指标进行meta分析,并根据研究人群种族不同进行亚组分析。结果本研究共纳入15篇文献,T2DM组和对照组病例数分别为24 315例和35 132例。Meta分析显示,CDKAL1基因rs7756992位点A>G多态性与T2DM易感性有关联[等位基因模式(G vs A):OR=1.171,95%CI1.122~1.223,P<0.001;共显性模式(GG vs AA):OR=1.380,95%CI1.258~1.515,P<0.001;共显性模式(AG vs AA):OR=1.131,95%CI 1.089~1.176,P<0.001;显性模式(AG+GG vs AA):OR=1.168,95%CI 1.101~1.240,P<0.001;隐性模式(GG vs AA+AG):OR=1.343,95%CI 1.282~1.405,P<0.001]。亚组分析显示,亚洲人群和白种人群中携带CDKAL1基因rs7756992位点G等位基因的人群发生T2DM的风险增加(P<0.05);而非洲人群中携带CDKAL1基因rs7756992位点G等位基因与A等位基因的人群发生T2DM风险的差异无统计学意义。结论在亚洲人群及白种人群中CDKAL1基因rs7756992位点A>G等位基因的突变可能是T2DM发病的危险因素之一。
基金Supported by A grant from Samsung Biomedical Research Institute,No.C-A9-210-1
文摘AIM:To evaluate the expression status of S-phase kinase-associated protein 2(Skp2)/cyclin-dependent kinases regulatory subunit 1(Cks1)and p27kip1,and assess the prognostic significance of Skp2/Cks1 expression with p27kip1in patients with extrahepatic cholangiocarcinoma.METHODS:Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December1994 to March 2008 were enrolled.Immunohistochemical staining for Skp2,Cks1,p27kip1,and Ki67,along with other relevant molecular biologic experiments,were performed.RESULTS:By Cox regression analyses,advanced age(>65 years),advanced AJCC tumor stage,poorly differentiated histology,and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic cholangiocarcinoma.Exogenous epidermal growth factor(EGF,especially 0.1-10 ng/mL)significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27kip1in SNU-1196,SNU-1079,and SNU-245 cells.The protein levels of Skp2/Cks1(from nuclear lysates)and p27kip1(from cytosolic lysate)were also significantly increased in these cells.There were significant reductions in the protein levels of Skp2/Cks1and p27kip1(from nuclear lysate)after the treatment of LY294002.By chromatin immunoprecipitation assay,we found that E2F1 transcription factor directly binds to the promoter site of Skp2.CONCLUSION:Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic cholangiocarcinoma.EGF upregulates the mRNA and protein levels of Skp2/Cks1and p27kip1via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter.
