Genetic variability within the cholesterol lowering pathway and the effectiveness of statins in reducing the risk of MI

Autor: Bruce M. Psaty, J. C. Bis, Olaf H. Klungel, Anke-Hilse Maitland-van der Zee, Nicole L. Glazer, Bas J M Peters, Helmi Pett, Bruno H. Stricker, Anthonius de Boer, Kerri L. Wiggins
Přispěvatelé: Epidemiology, Cardiology
Rok vydání: 2011
Předmět:
Male
Myocardial Infarction
Pharmacology
Risk Factors
Odds Ratio
Registries
ATP Binding Cassette Transporter
Subfamily G
Member 5
Netherlands
education.field_of_study
Serine Endopeptidases
Middle Aged
Scavenger Receptors
Class B
Cholesterol
Phenotype
Treatment Outcome
Population study
Female
Proprotein Convertases
Proprotein Convertase 9
Cardiology and Cardiovascular Medicine
Low Density Lipoprotein Receptor-Related Protein-1
medicine.medical_specialty
Statin
Genotype
medicine.drug_class
Lipoproteins
Hypercholesterolemia
Population
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
Risk Assessment
Article
Internal medicine
medicine
Humans
education
Aged
Chi-Square Distribution
PCSK9
Case-control study
Lipase
Odds ratio
PPAR gamma
Logistic Models
Pharmacogenetics
Case-Control Studies
ATP-Binding Cassette Transporters
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Sterol O-Acyltransferase
Zdroj: Atherosclerosis, 217(2), 458-464. Elsevier Ireland Ltd
ISSN: 1879-1484
0021-9150
1088-8896
Popis: Genetic variability has been shown to affect statin responsiveness. Participants from the Utrecht Cardiovascular Pharmacogenetics (UCP) studies were enrolled from a population-based registry of pharmacy records linked to hospital discharge records (PHARMO) to investigate tagging SNPs within candidate genes involved in the cholesterol lowering pathway for modification of the effectiveness of statins in reducing the risk of myocardial infarction (MI). Patients who received a prescription for an antihypertensive drug and/or had hypercholesterolemia were selected from the PHARMO database. We designed a nested case-control study in which cases were hospitalized for MI and controls were not. Patients were contacted through their community pharmacies. For this study, only hypercholesterolemic participants were selected. Logistic regression analysis was used to investigate pharmacogenetic interactions. The Heart and Vascular Health Study (HVH) was used to replicate findings from UCP. The study population included 668 cases and 1217 controls. We selected 231 SNPs of which 209 SNPs in 27 genes passed quality control. Ten SNPs in eight genes were found to influence the effectiveness of statins in UCP, of which the most significant interaction was found with SCARB1 rs4765615. Other genes that reached statistical significance (p < 0.05) included two SNPs in PCSK9 (rs10888896 and rs505151 (E670G)), two SNPs in ABCG5 (rs4245786 and rs1864815), LIPC rs16940379, ABCA1 rs4149264, PPARG rs2972164, LRP1 rs715948, and SOAT1 rs2493121. None of the total of 5 SNPs that were available for replication in HVH reached statistical significance. In conclusion, ten SNPs were found to modify the effectiveness of statins in reducing the risk of MI in the UCP study. Five were also tested in the HVH study, but no interactions reached statistical significance. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
Databáze: OpenAIRE
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