Functional analysis of LDLR promoter and 5' UTR mutations in subjects with clinical diagnosis of familial hypercholesterolemia.

摘要: Familial hypercholesterolemia (FH) is a dominant disorder due to mutations in the LDLR gene. Several promoter are associated with FH. Screening of 3,705 Spanish FH patients identified 10 variants and 5 0 UTR. Here, we analyse functionality six newly variants. Mutations located regulatory elements R2 R3 (c.� 155_-150delACCCCinsTTCTG- CAAACTCCTCCC, c.� 136C4G, 140C4G, 140C4T) resulted 6 15% residual activity reporter expression experiments changes nuclear protein binding affinity compared wild type. No reduction was observed when cells were transfected 208T, 88A, 36G mutant fragments. Our results indicate that localized hypercholesterolemia, whereas outside response not cause This data emphasizes importance functional analysis determine their association phenotype. Hum Mutat 32:868-872, 2011. & 2011 Wiley-Liss, Inc.