on April 12, 2007
Published online before print April 12, 2007, doi: 10.1161/ATVBAHA.107.140103
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Submitted on October 25, 2006
Accepted on March 28, 2007
Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants. The GOLDN Study
Chao-Qiang Lai *;
From the Nutrition and Genomics Laboratory (C.-Q.L., X.A., L.D.P., J.M.O.), JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; the Department of Epidemiology (D.K.A.), University of Alabama at Birmingham; the School of Medicine (D.C.), University of Valencia, Spain; the Department of Experimental and Clinical Pharmacology, College of Pharmacy (R.J.S.), the Department of Laboratory Medicine and Pathology (M.Y.T.), and the Division of Epidemiology and Community Health (J.M.P.), University of Minnesota, Minneapolis; the Human Genetics Center (J.E.H.), University of Texas, Houston; and the Division of Biostatistics (M.A.P.), Washington University School of Medicine, Saint Louis, Mo.
* To whom correspondence should be addressed. E-mail: chao.lai{at}tufts.edu.
Objective--Apolipoprotein A5 (APOA5) is a key determinant of plasma triglyceride (TG) concentrations. Genetic variation at the APOA5 locus could be responsible for some of the observed differences in response to fenofibrate therapy.
Methods and Results--We examined the association between tag SNPs (-1131T>C and 56C>G) at APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge in 791 men and women participating in the GOLDN study. After 3-week drug treatment, APOA5 56G carriers displayed significant decrease in TG (P=0.006), and increase in HDL-C (P=0.002) levels relative to their basal values in the fasting state when compared with noncarriers (a TG reduction of -35.8±2.8% versus -27.9±0.9% and a HDL-C increase of 11.8±1.3% versus 6.9±0.5%, respectively). In the postprandial lipemia after a fat load, the 56G carriers showed a significant decrease in the area under curve for TG and increase for HDL-C than the noncarriers. These diverse beneficial responses of 56G carriers to fenofibrate were further characterized by a higher increase in large LDL-C concentrations and LDL size. On the other hand, subjects with different APOA5-1131T>C genotypes showed no significant response to fenofibrate intervention.
Conclusion--This study suggests that the APOA5 56G carriers benefited more from the fenofibrate treatment than noncarriers in lowering plasma TG and increasing HDL-C levels.
Key words: APOA5 • fenofibrate • triglyceride lowering • increasing HDL-C • gene-drug interaction
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