title: Scavenger receptor class B type I protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia.
abstract: BACKGROUND
  In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol (HDL-C) levels.
  
  
  OBJECTIVE
  Our objective was to determine the relationship between SR-BI protein and HDL-C levels in humans.
  
  
  METHODS
  This was a prospective study of adults with hyperalphalipoproteinemia. Fasting blood was obtained for lipid and lipoprotein measurement, genomic DNA, and monocyte-derived macrophages. SR-BI protein levels were measured by Western blots, and SR-BI activity was measured by cholesteryl ester (CE) uptake of each donor's radiolabeled HDL with their monocyte-derived macrophages, or by degradation and specific cell association of dual-labeled HDL in vitro.
  
  
  METHODS
  The study was performed in a tertiary university teaching hospital.
  
  
  RESULTS
  The mean age was 57.2 +/- 10.9 yr (n = 65). SR-BI protein levels were inversely associated with HDL-C levels (P < 0.002), HDL particle size (P < 0.05), and positively associated with CE uptake (P < 0.004); there was no association with plasma apolipoprotein levels. SR-BI protein levels (P = 0.01) were independent predictors of HDL-C levels. Subjects who were carriers of the A allele for the rs4238001 (glycine to serine at position 2) polymorphism [single nucleotide polymorphism (SNP)] had lower SR-BI protein levels (P = 0.01), whereas carriers of the C allele for the rs2278986 SNP also had lower SR-BI protein levels (P = 0.02). Body mass index (P = 0.05), rs4238001 (P = 0.01), and rs2278986 (P = 0.01) SNPs were independent predictors of SR-BI protein levels. In vitro studies of murine macrophages stably expressing the glycine to serine at position 2 SNP showed less degradation (P < 0.0004) and specific cell association (P < 0.0004) of [(125)I, (3)H]-CE-labeled HDL.
  
  
  CONCLUSIONS
  SR-BI protein has an independent effect on HDL-C levels in women with hyperalphalipoproteinemia. Two SNPs were significantly associated with lower SR-BI protein levels.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: West
authors.forename: Erin
authors.initials: E
authors.lastname: Greason
authors.forename: Antonina
authors.initials: A
authors.lastname: Kolmakova
authors.forename: Anisa
authors.initials: A
authors.lastname: Jahangiri
authors.forename: Bela
authors.initials: B
authors.lastname: Asztalos
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Annabelle
authors.initials: A
authors.lastname: Rodriguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood* / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D044469:Racial Groups / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B