The Effects Of Polymorphisms In Ldlr 3′ -utr On Ldlr Expression Treated With Bbr

Objective BBR is used on clinical practice widely as an novel cholesterol lowering drug. BBR increases the half-life of Low density lipoprotein receptor mRNA through effects on a 1100 bp proximal section of the 3′untranslated region(3′UTR) and increases the expression of LDLR. BBR can lower cholesterol well. However, It can not lower every hypercholesterolemic-patient′s cholesterol level. In this study, we tested whether there are single nucleotide polymorphisms (SNPs) in the 3′UTR of LDLR that might affect LDLR expression and response to BBR treatment. Methods 113 hyperlipoidemia patients and 120 normaoipidemic subjects 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(TypeⅠ,Ⅱ,Ⅲ,Ⅳ,V)was used to detect the change of LDLR expression in HepG2 cells transfected with the above vectors.Results There are six SNPs(G44243A, G44332A, C44506G, G44695A, C44857T, A44964G) in LDLR 3′UTR and five SNP genotypes in LDLR 3′UTR of Chinese population. There is no another SNP in LDLR 3′UTR. 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(TypeⅠ,Ⅱ,Ⅲ,Ⅳ,V). Conclusions1. The SNPs(G44243A, G44332A, C44506G, G44695A, C44857T, A44964G) in LDLR 3′UTR could not affect the blood lipid level(P>0.05).2. 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.