Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men
| Autor: | Anders Hamsten, Ewa Ehrenborg, Christopher J. Packard, Fredrik Karpe, Josefin Skogsberg, Alex D. McMahon |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Genotype Hypercholesterolemia Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor Coronary Disease Disease chemistry.chemical_compound Risk Factors Diabetes mellitus Internal medicine Internal Medicine medicine Humans Genetic Predisposition to Disease chemistry.chemical_classification Polymorphism Genetic Anthropometry Cholesterol business.industry Cholesterol HDL Case-control study Cholesterol LDL Middle Aged medicine.disease Endocrinology chemistry Case-Control Studies lipids (amino acids peptides and proteins) Peroxisome proliferator-activated receptor delta business Pravastatin Transcription Factors Lipoprotein medicine.drug |
| Zdroj: | Journal of Internal Medicine. 254:597-604 |
| ISSN: | 1365-2796 0954-6820 |
| Popis: | Skogsberg J, McMahon AD, Karpe F,Hamsten A, Packard CJ, Ehrenborg E, on behalf ofthe West of Scotland Coronary Prevention Study(Atherosclerosis Research Unit, King Gustaf VResearch Institute, Karolinska Hospital, Stockholm,Sweden; Robertson Centre for Biostatistics,University of Glasgow, Glasgow, UK; Oxford Centrefor Diabetes, Endocrinology and Metabolism, Oxford,UK; and Glasgow Royal Infirmary University NHSTrust, Glasgow, UK). Peroxisome proliferatoractivated receptor delta genotype in relation tocardiovascular risk factors and risk of coronaryheart disease in hypercholesterolaemic men. J InternMed 2003; 254: 597–604.Objectives. Peroxisome proliferator activatedreceptor delta (PPARD) is a transcription factorimplicated in the regulation of genes involved incholesterol metabolism. We recently discovered acommon polymorphism in the 5¢-untranslatedregion (5¢-UTR) of the human PPARD, +294T/C,that is associated with an increased plasma low-density lipoprotein cholesterol (LDL-C) concentrationin healthy subjects. Whether the +294C allele isassociated with LDL-C elevation independently of thebackground lipoprotein phenotype and whether itconfers increased risk of coronary heart disease(CHD) is unknown. Against this background, weinvestigated the relationships between thePPARD polymorphism and plasma lipoproteinconcentrations and the risk for contracting CHD inthe West of Scotland Coronary Prevention Study(WOSCOPS).Design. A nested case–control study of participantsin a randomized double-blind placebo-controlledtrial of pravastatin in mildly-to-moderatelyhypercholesterolaemic men.Subjects. A total of 580 cases of incident CHD and1160 individuals who remained free of CHD(controls).Main outcome measures. Plasma lipoprotein con-centrations and risk of CHD according to PPARDgenotype.Results. Individuals carrying the rare PPARD+294C allele had a significantly lower high-densitylipoprotein cholesterol (HDL-C) concentration thansubjects homozygous for the common T-allele.Homozygous carriers of the C-allele also showed atendency towards higher risk of CHD compared withhomozygous carriers of the T-allele. In addition, agene–gene interaction involving the PPARDpolymorphism and the PPAR alpha L162Vpolymorphism may influence the plasma LDL-Cconcentration.Conclusions. PPARD plays a role in cholesterolmetabolism in man.Keywords: association study, cholesterol metabo-lism, coronary heart disease, peroxisome proliferatoractivated receptor delta, polymorphism. |
| Databáze: | OpenAIRE |
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