Document Detail


Apolipoprotein E polymorphisms and postprandial triglyceridemia before and after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study.
MedLine Citation:
PMID:  20729559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Although much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate.
METHODS AND RESULTS: We evaluated the effects of the APOE locus on fasting and postprandial triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study. Participants were evaluated after a high-fat meal challenge before (n=1072) and after 3 weeks of daily treatment with 160 mg of fenofibrate (n=738). Mixed models adjusted for sex, age, waist circumference, and family relationship were used to examine the association of the ε4 carrier and ε2 carrier status versus ε3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared with the ε3/ε3 genotype, ε2 carriers had on average higher fasting triglyceride concentrations (130.5 mg/dL versus 109.3 mg/dL, P<0.001). After fenofibrate treatment, the APOE genotype differences persisted in the fasting state (ε2 carriers: 85.1 mg/dL versus ε3/ε3: 75.9 mg/dL, P<0.05). Carriers of the ε4 allele had significantly higher fasting triglyceride concentrations only prefenofibrate (120.9 mg/dL versus 109.3 mg/dL, P=0.008). APOE alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for ε2 carriers versus ε3 homozygotes (but not ε4 carriers) both before and after fenofibrate treatment (P=0.01 and P=0.005, respectively).
CONCLUSIONS: APOE polymorphisms are important determinants of triglyceride concentrations, especially in the fasting state.
Authors:
Marguerite R Irvin; Edmond K Kabagambe; Hemant K Tiwari; Laurence D Parnell; Robert J Straka; Michael Tsai; Jose M Ordovas; Donna K Arnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-21
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  3     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2011-01-31     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-7     Citation Subset:  IM    
Affiliation:
Department of Epidemiology, University of Alabama at Birmingham, USA. irvinr@uab.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Apolipoproteins E / genetics*
Dietary Fats / metabolism
Fasting
Female
Fenofibrate / therapeutic use*
Genotype
Humans
Hyperlipidemias / drug therapy*
Hypolipidemic Agents / therapeutic use*
Middle Aged
Polymorphism, Genetic*
Postprandial Period / physiology*
Triglycerides / blood*
Grant Support
ID/Acronym/Agency:
T32NS054584/NS/NINDS NIH HHS; U01 HL072524-04/HL/NHLBI NIH HHS; U01HL072524-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Dietary Fats; 0/Hypolipidemic Agents; 0/Triglycerides; 49562-28-9/Fenofibrate
Comments/Corrections
Comment In:
Circ Cardiovasc Genet. 2011 Feb;4(1):e5; author reply e6   [PMID:  21325156 ]

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