Association between a novel 11-base pair deletion mutation in the promoter region of the scavenger receptor class B type I gene and plasma HDL cholesterol levels in Taiwanese Chinese.
Journal - Arteriosclerosis, thrombosis, and vascular biology (United States )
OBJECTIVE: Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels. METHODS AND RESULTS: We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCCGT deletion mutation from positions -140 to -150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C-->T substitution at position -142. Twenty-six of 690 unrelated subjects were heterozygous for the -140 to -150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the -140 to -150 deletion mutation was significantly associated with increased HDL-C levels and explained approximately 0.5% of the variation in HDL-C levels in this population. CONCLUSIONS: A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.
|ISSN : ||1524-4636|
|Mesh Heading : ||Antigens, CD36 Asian Continental Ancestry Group Base Pairing Base Sequence Cholesterol, HDL DNA Mutational Analysis Electrophoretic Mobility Shift Assay Female Humans Hypercholesterolemia Linear Models Male Middle Aged Point Mutation Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Single-Stranded Conformational Promoter Regions, Genetic Receptors, Scavenger Scavenger Receptors, Class B Taiwan genetics ethnology genetics genetics|
|Mesh Heading Relevant : ||Membrane Proteins Receptors, Immunologic Receptors, Lipoprotein Sequence Deletion genetics blood|