Genetic determinants of plasma HDL-cholesterol levels in familial hypercholesterolemia
| Autor: | Angelique C.M. Jansen, Michael W.T. Tanck, John J.P. Kastelein, Joep C. Defesche, Emily S. van Aalst-Cohen, Marcel Fontecha, S. Matthijs Boekholdt, Suzanne Cheng, Jan Albert Kuivenhoven, Jia Li |
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| Přispěvatelé: | Cardiology, Vascular Medicine, APH - Amsterdam Public Health, Epidemiology and Data Science, ACS - Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Apolipoprotein E
Adult Male medicine.medical_specialty Apolipoprotein B Alcohol Drinking Genotype Familial hypercholesterolemia Biology Body Mass Index Cohort Studies Hyperlipoproteinemia Type II chemistry.chemical_compound Sex Factors Internal medicine Cholesterylester transfer protein Genetics medicine Humans Apolipoproteins C Genetics (clinical) Apolipoproteins A Glycoproteins Lipoprotein lipase Apolipoprotein C-III Polymorphism Genetic Cholesterol Cholesterol HDL Smoking Middle Aged medicine.disease Cholesterol Ester Transfer Proteins Lipoprotein Lipase Endocrinology chemistry biology.protein ATP-Binding Cassette Transporters Female lipids (amino acids peptides and proteins) Hepatic lipase Carrier Proteins Lipoprotein ATP Binding Cassette Transporter 1 |
| Zdroj: | European journal of human genetics, 13(10), 1137-1142. Nature Publishing Group |
| ISSN: | 1018-4813 |
| Popis: | The objective of this study was to determine the extent to which common genetic variants can explain the variation of high-density lipoprotein cholesterol (HDL-C) plasma levels in familial hypercholesterolemia (FH). FH is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). Although low HDL-C levels have been shown to affect the severity of the clinical phenotype, little is known about the factors that determine HDL-C levels in these patients. A cohort of 1002 heterozygous FH patients was genotyped for polymorphisms in the genes encoding for ATP-binding cassette transporter A1, apolipoprotein (apo) AIV, apoCIII, apoE, cholesteryl transfer ester protein, hepatic lipase, lipoprotein lipase, and two paraoxonases. Multiple linear regression showed that, together, these polymorphisms explain only 3.9% of the variation of HDL-C plasma levels. When significant two-way interactions between the polymorphisms were also taken into account, the explained variation rose to 12.5%. In a regression model that also incorporated sex, smoking, alcohol use, body mass index, and concomitant beta-blocker use as covariates, the explained variation of HDL-C plasma levels even increased to 32.5%. This study provides direct evidence that multiple, modestly penetrant, but highly prevalent, polymorphisms can explain a substantial part of the variation of HDL-C plasma levels in a representative large cohort of heterozygous FH patients. |
| Databáze: | OpenAIRE |
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