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Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia
- Source :
- Nutrition Metabolism and Cardiovascular Diseases, 23(11), 1115-1121. ELSEVIER SCI LTD, Nutrition Metabolism and Cardiovascular Diseases, 23, 11, pp. 1115-21, Nutrition Metabolism and Cardiovascular Diseases, 23, 1115-21
- Publication Year :
- 2013
-
Abstract
- Item does not contain fulltext BACKGROUND AND AIMS: Two recent independent studies showed that patients with familial combined hyperlipidemia (FCHL) have elevated plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) and markers of cholesterol synthesis. Both PCSK9 expression and cholesterol synthesis are downstream effects of hepatic activation of sterol regulatory element binding protein 2 (SREBP2). The present study was conducted to study the relationship between plasma PCSK9 and markers of cholesterol synthesis in FCHL. METHODS AND RESULTS: Markers of cholesterol synthesis (squalene, desmosterol, lathosterol), cholesterol absorption (campesterol, sitosterol, cholestanol) and PCSK9 were measured in plasma of FCHL patients (n = 103) and their normolipidemic relatives (NLR; n = 240). Plasma PCSK9, lathosterol and desmosterol levels were higher in FCHL patients than their NLR (p < 0.001, age and sex adjusted). Heritability calculations demonstrated that 35% of the variance in PCSK9 levels could be explained by additive genetic effects (p < 0.001). Significant age- and sex-adjusted correlations were observed for the relationship between PCSK9 and lathosterol, both unadjusted and adjusted for cholesterol, in the overall FCHL population (both p < 0.001). Multivariate regression analyses, with PCSK9 as the dependent variable, showed that the regression coefficient for FCHL status decreased by 25% (from 0.8 to 0.6) when lathosterol was included. Nevertheless, FCHL status remained an independent contributor to plasma PCSK9 (p < 0.001). CONCLUSIONS: The present study confirms the previously reported high and heritable PCSK9 levels in FCHL patients. Furthermore, we now show that high PCSK9 levels are, in part, explained by plasma lathosterol, suggesting that SREBP2 activation partly accounts for elevated PCSK9 levels in FCHL.
- Subjects :
- Adult
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Campesterol
Hyperlipidemia, Familial Combined
Medicine (miscellaneous)
Lathosterol
Models, Biological
LDL
Cohort Studies
PCSK9
chemistry.chemical_compound
Isomerism
Internal medicine
Desmosterol
medicine
Humans
Family
Health aging / healthy living Cardiovascular diseases [IGMD 5]
Netherlands
Nutrition and Dietetics
Chemistry
Cholestanol
Serine Endopeptidases
Reproducibility of Results
Middle Aged
Proprotein convertase
Up-Regulation
Endocrinology
Lipid metabolism
Cholesterol
Multivariate Analysis
Regression Analysis
Kexin
FCHL
Female
Proprotein Convertases
Sterol regulatory element-binding protein 2
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 09394753
- Database :
- OpenAIRE
- Journal :
- Nutrition Metabolism and Cardiovascular Diseases, 23(11), 1115-1121. ELSEVIER SCI LTD, Nutrition Metabolism and Cardiovascular Diseases, 23, 11, pp. 1115-21, Nutrition Metabolism and Cardiovascular Diseases, 23, 1115-21
- Accession number :
- edsair.doi.dedup.....8de80e4abb754509a870ca60c2871504