Abstract

Context: PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease. PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized. Objective: The aim of the study was to measure PCSK9 levels in a large, ethnically diverse population (n = 3138) utilizing a sensitive and specific sandwich ELISA. Design: We conducted an observational study in the Dallas Heart Study, a multiethnic, probability based sample of Dallas County. Results: Plasma levels of PCSK9 varied over approximately 100-fold range (33-2988 ng/ml; median, 487 ng/ml). Levels were significantly higher in women (517 ng/ml) than in men (450 ng/ml), and in postmenopausal women compared to premenopausal women (P < 0.0001), irrespective of estrogen status. Plasma levels of PCSK9 correlated with plasma levels of LDL-C (r = 0.24) but explained less than 8% of the variation in LDL-C levels (r2 = 0.073). Other factors that correlated with PCSK9 levels included plasma levels of triglycerides, insulin, and glucose. Individuals with loss-of-function mutations in PCSK9 and reduced plasma levels of LDL-C also had significantly lower plasma levels of PCSK9 after adjusting for age, gender, and LDL-C levels (P < 0.0001). Conclusion: Multiple metabolic and genetic factors contribute to variation in plasma levels of PCSK9 in the general population. Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein.

Original languageEnglish (US)
Pages (from-to)2537-2543
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number7
DOIs
StatePublished - Jul 2009

Fingerprint

Plasmas
LDL Cholesterol
Lipoproteins
Plasma (human)
Sampling Studies
Population
Observational Studies
Coronary Disease
Blood Proteins
Estrogens
Triglycerides
Enzyme-Linked Immunosorbent Assay
Insulin
Glucose
Mutation
Proteins

ASJC Scopus subject areas

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

Cite this

Genetic and metabolic determinants of plasma PCSK9 levels. / Lakoski, Susan G.; Lagace, Thomas A.; Cohen, Jonathan C.; Horton, Jay D.; Hobbs, Helen H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 7, 07.2009, p. 2537-2543.

Research output: Contribution to journalArticle

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abstract = "Context: PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease. PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized. Objective: The aim of the study was to measure PCSK9 levels in a large, ethnically diverse population (n = 3138) utilizing a sensitive and specific sandwich ELISA. Design: We conducted an observational study in the Dallas Heart Study, a multiethnic, probability based sample of Dallas County. Results: Plasma levels of PCSK9 varied over approximately 100-fold range (33-2988 ng/ml; median, 487 ng/ml). Levels were significantly higher in women (517 ng/ml) than in men (450 ng/ml), and in postmenopausal women compared to premenopausal women (P < 0.0001), irrespective of estrogen status. Plasma levels of PCSK9 correlated with plasma levels of LDL-C (r = 0.24) but explained less than 8{\%} of the variation in LDL-C levels (r2 = 0.073). Other factors that correlated with PCSK9 levels included plasma levels of triglycerides, insulin, and glucose. Individuals with loss-of-function mutations in PCSK9 and reduced plasma levels of LDL-C also had significantly lower plasma levels of PCSK9 after adjusting for age, gender, and LDL-C levels (P < 0.0001). Conclusion: Multiple metabolic and genetic factors contribute to variation in plasma levels of PCSK9 in the general population. Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein.",
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T1 - Genetic and metabolic determinants of plasma PCSK9 levels

AU - Lakoski, Susan G.

AU - Lagace, Thomas A.

AU - Cohen, Jonathan C.

AU - Horton, Jay D.

AU - Hobbs, Helen H.

PY - 2009/7

Y1 - 2009/7

N2 - Context: PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease. PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized. Objective: The aim of the study was to measure PCSK9 levels in a large, ethnically diverse population (n = 3138) utilizing a sensitive and specific sandwich ELISA. Design: We conducted an observational study in the Dallas Heart Study, a multiethnic, probability based sample of Dallas County. Results: Plasma levels of PCSK9 varied over approximately 100-fold range (33-2988 ng/ml; median, 487 ng/ml). Levels were significantly higher in women (517 ng/ml) than in men (450 ng/ml), and in postmenopausal women compared to premenopausal women (P < 0.0001), irrespective of estrogen status. Plasma levels of PCSK9 correlated with plasma levels of LDL-C (r = 0.24) but explained less than 8% of the variation in LDL-C levels (r2 = 0.073). Other factors that correlated with PCSK9 levels included plasma levels of triglycerides, insulin, and glucose. Individuals with loss-of-function mutations in PCSK9 and reduced plasma levels of LDL-C also had significantly lower plasma levels of PCSK9 after adjusting for age, gender, and LDL-C levels (P < 0.0001). Conclusion: Multiple metabolic and genetic factors contribute to variation in plasma levels of PCSK9 in the general population. Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein.

AB - Context: PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease. PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized. Objective: The aim of the study was to measure PCSK9 levels in a large, ethnically diverse population (n = 3138) utilizing a sensitive and specific sandwich ELISA. Design: We conducted an observational study in the Dallas Heart Study, a multiethnic, probability based sample of Dallas County. Results: Plasma levels of PCSK9 varied over approximately 100-fold range (33-2988 ng/ml; median, 487 ng/ml). Levels were significantly higher in women (517 ng/ml) than in men (450 ng/ml), and in postmenopausal women compared to premenopausal women (P < 0.0001), irrespective of estrogen status. Plasma levels of PCSK9 correlated with plasma levels of LDL-C (r = 0.24) but explained less than 8% of the variation in LDL-C levels (r2 = 0.073). Other factors that correlated with PCSK9 levels included plasma levels of triglycerides, insulin, and glucose. Individuals with loss-of-function mutations in PCSK9 and reduced plasma levels of LDL-C also had significantly lower plasma levels of PCSK9 after adjusting for age, gender, and LDL-C levels (P < 0.0001). Conclusion: Multiple metabolic and genetic factors contribute to variation in plasma levels of PCSK9 in the general population. Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein.

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U2 - 10.1210/jc.2009-0141

DO - 10.1210/jc.2009-0141

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VL - 94

SP - 2537

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JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

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