低密度脂蛋白受体3′非翻译区单核苷酸多态性对黄连素调节低密度脂蛋白受体表达的影响  

The effects of polymorphisms in LDLR 3′-UTR on LDLR expression treated with BBR

作　　者：蒋华新[1] 何帮顺[1] 潘玉琴[1] 曾庆娣[1] 陈家梁[1] 王书奎[1] 

机构地区：[1]南京医科大学附属南京第一医院中心实验室,江苏南京210006

出　　处：《医学研究生学报》2009年第4期350-354,共5页Journal of Medical Postgraduates

基　　金：南京市医学科技发展项目(批准号:200603004)

摘　　要：目的:中药黄连素具有降低血清中低密度脂蛋白胆固醇(LDL-C)的作用,其作用机制是否与低密度脂蛋白受体(LDLR)的单核苷酸多态性(SNP)有关尚不清楚。现探讨LDLR3′非翻译区(LDLR 3-′UTR)的SNP对黄连素调节LDLR表达的影响。方法:收集113例高脂血症合并冠心病患者,提取外周血基因组DNA,检测LDLR 3′-UTR的SNP,分析LDLR 3-′UTR的基因型与中国人群血脂水平的关系。此外,构建了携带不同LDLR 3-′UTR基因型(TypeⅠ、Ⅱ、Ⅲ、Ⅳ、Ⅴ)的荧光素酶报告基因载体(pLuc),转染HepG2细胞后采用黄连素(Berberine,BBR)作用12h后观察pLuc的活性变化。结果:中国人群的LDLR 3-′UTR存在着Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ等SNP分布,但这些基因型频率与中国人群的血脂水平无明显相关性,携带有不同SNP基因型的荧光素酶报告基因载体转染HepG2细胞,在BBR作用后LDLR表达上调程度相似。结论:LDLR 3-′UTR的基因型频率及其分布的遗传性变异不能影响BBR对LDLR表达的上调作用,从而可为临床使用黄连素治疗高脂血症提供理论依据。Objective：Berberine（BBR）,a traditional Chinese medicine,exbibits the effect of reducing the level of low density lipoprotein cholesterol in serum,but it is still unclear if the mechanism correlates with the single nucleotide polymorphism（SNP） of LDLR.In this study the effect of SNP of LDLR 3′-UTR on LDLR expression in HepG2 cells treated with BBR was exptored.Methods：113 hyperlipoidemia patients with coronary heart disease were enrolled to isolate genomic DNA from peripheral blood.PCR-amplified was used to detect the single nucleotide polymorphisms（SNPs） and genotypes of LDLR 3′-UTR,and the relationship between the genotypes of LDLR 3′-UTR and lipid level of Chinese population was also investigated.In addition,incubated with BBR for 12h,luciferase report gene vector（pLuc） containing different types of LDLR 3′-UTR（Type Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ）was used to detect the change of LDLR expression in HepG2 cells transfected with the above vectors.Results：There are five SNP genotypes in LDLR 3′-UTR of Chinese population,however,the SNP genotypes were not related with the lipid levels.There were not significant difference of LDLR expression of HepG2 cells treated with BBR after being transfected with pLuc vectors containing different types of LDLR 3′-UTR（Type Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ）.Conclusion：The frequency and genetic variation of LDLR 3′-UTR genotypes could not diminish the LDLR highering effect of BBR,so that the research could provide theorical evidence for the application of BBR to treat hyperlipoidemia in clinical practice.

关 键 词：低密度脂蛋白受体3′非翻译区 单核苷酸多态性 黄连素 

分 类 号：Q754[生物学—分子生物学]