title: A synonymous variant in scavenger receptor, class B, type I gene is associated with lower SR-BI protein expression and function.
abstract: OBJECTIVE
  A synonymous variant within scavenger receptor class B type I gene (SCARB1), exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans. The objective was to determine if rs5888 decreased SR-BI protein expression and function in vitro.
  
  
  METHODS
  SR-BI RNA secondary structure, turnover, polysomal distribution and protein expression were examined in COS cells transfected with wild-type or rs5888-SR-BI plasmids by selective 2'-hydroxyl acylation and primer extension assays, actinomycin D inhibition, polysomal profiling, and western blotting. SR-BI function in murine macrophages stably expressing wild-type or rs5888-SR-BI was assessed by measuring the specific cell association of (125)I,(3)H-cholesteryl ester (CE) radiolabeled HDL.
  
  
  RESULTS
  Rs5888 changed RNA secondary structure and led to marked differences in the polysomal profiles compared with wild-type transcript (p<0.02). As compared to wild-type cells, COS cells expressing rs5888 had significantly lower SR-BI protein expression (p<0.04), but no difference in total RNA transcript levels. There were no differences in SR-BI RNA turnover in murine macrophages, whereas specific cell association of (125)I (p<0.0001) or (3)H-CE (p<0.00001) was significantly lower in rs5888 cells.
  
  
  CONCLUSIONS
  The rs5888 variant affected SR-BI RNA secondary structure, protein translation, and was significantly associated with reduced SR-BI protein expression and function in vitro.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Constantineau
authors.forename: Erin
authors.initials: E
authors.lastname: Greason
authors.forename: Michael
authors.initials: M
authors.lastname: West
authors.forename: Megan
authors.initials: M
authors.lastname: Filbin
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kieft
authors.forename: Martha Z
authors.initials: MZ
authors.lastname: Carletti
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
authors.forename: Annabelle
authors.initials: A
authors.lastname: Rodriguez
mesh_terms: D005091:Exons; D006801:Humans; D008264:Macrophages / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D012313:RNA / Q000737:chemistry; D051122:Scavenger Receptors, Class B / Q000032:analysis* / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D012313:RNA