Scavenger receptor class B type i protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia

Michael West, Erin Greason, Antonina Kolmakova, Anisa Jahangiri, Bela Asztalos, Toni I. Pollin, Annabelle Rodriguez

Research output: Contribution to journalArticle

Abstract

Context: 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. Design: 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. Setting: 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 [ 125I, 3H]-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.

LanguageEnglish (US)
Pages1451-1457
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number4
DOIs
StatePublished - Apr 2009

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Class B Scavenger Receptors
CD36 Antigens
HDL Cholesterol
HDL Lipoproteins
Single Nucleotide Polymorphism
Proteins
Polymorphism
Cholesterol Esters
Macrophages
Nucleotides
Association reactions
Glycine
Serine
Cholesteryl Ester Transfer Protein Deficiency
Alleles
Degradation
Protein Deficiency
Apolipoproteins
Particle Size
Tertiary Care Centers

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Scavenger receptor class B type i protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia. / West, Michael; Greason, Erin; Kolmakova, Antonina; Jahangiri, Anisa; Asztalos, Bela; Pollin, Toni I.; Rodriguez, Annabelle.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 4, 04.2009, p. 1451-1457.

Research output: Contribution to journalArticle

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abstract = "Context: 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. Design: 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. Setting: 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 [ 125I, 3H]-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.",
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T1 - Scavenger receptor class B type i protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia

AU - West,Michael

AU - Greason,Erin

AU - Kolmakova,Antonina

AU - Jahangiri,Anisa

AU - Asztalos,Bela

AU - Pollin,Toni I.

AU - Rodriguez,Annabelle

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N2 - Context: 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. Design: 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. Setting: 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 [ 125I, 3H]-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.

AB - Context: 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. Design: 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. Setting: 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 [ 125I, 3H]-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.

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