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A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies
- Publication Year :
- 2016
- Publisher :
- The University of North Carolina at Chapel Hill University Libraries, 2016.
-
Abstract
- Fibrates are commonly prescribed for hypertriglyceridemia, but they also lower LDL cholesterol and increase HDL cholesterol. Large interindividual variations in lipid response suggest that some patients may benefit more than others and genetic studies could help identify such patients.We carried out the first genome-wide association study of lipid response to fenofibrate using data from two well-characterized clinical trials: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study. Genome-wide association study data from both studies were imputed to the 1000 Genomes CEU reference panel (phase 1). Lipid response was modeled as the log ratio of the post-treatment lipid level to the pretreatment level. Linear mixed models (GOLDN, N=813 from 173 families) and linear regression models (ACCORD, N=781) adjusted for pretreatment lipid level, demographic variables, clinical covariates, and ancestry were used to evaluate the association of genetic markers with lipid response. Among Caucasians, the results were combined using inverse-variance weighted fixed-effects meta-analyses. The main findings from the meta-analyses were examined in other ethnic groups from the HyperTG study (N=267 Hispanics) and ACCORD (N=83 Hispanics, 138 African Americans).A known lipid locus harboring the pre-B-cell leukemia homeobox 4 (PBX4) gene on chromosome 19 is important for LDL cholesterol response to fenofibrate (smallest P=1.5×10). The main results replicated with nominal statistical significance in Hispanics from ACCORD (P0.05).Future research should evaluate the usefulness of this locus to refine clinical strategies for lipid-lowering treatments.
- Subjects :
- 0301 basic medicine
Genetic Markers
Male
Genotype
Genome-wide association study
030204 cardiovascular system & hematology
Biology
Pharmacology
Article
White People
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Fenofibrate
Meta-Analysis as Topic
Outcome Assessment, Health Care
Genetics
medicine
Humans
General Pharmacology, Toxicology and Pharmaceutics
Molecular Biology
Genetics (clinical)
Hypolipidemic Agents
Hypertriglyceridemia
Clinical Trials as Topic
Triglyceride
Cholesterol
nutritional and metabolic diseases
Lipid metabolism
Middle Aged
medicine.disease
Lipid Metabolism
Lipids
030104 developmental biology
chemistry
Molecular Medicine
Female
lipids (amino acids, peptides, and proteins)
Dyslipidemia
medicine.drug
Lipoprotein
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....51bbdae09847be01c80822eec11056cc
- Full Text :
- https://doi.org/10.17615/r998-ha33