Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 27 Số 6 - Trang 1417-1425 - 2007
Chao‐Qiang Lai1,2,3,4,5,6, Donna K. Arnett1,2,3,4,5,6, Dolores Corella1,2,3,4,5,6, Robert J. Straka1,2,3,4,5,6, Michael Y. Tsai1,2,3,4,5,6, James M. Peacock1,2,3,4,5,6, Xian Adiconis1,2,3,4,5,6, Laurence D. Parnell1,2,3,4,5,6, James E. Hixson1,2,3,4,5,6, Michael A. Province1,2,3,4,5,6, José M. Ordovás1,2,3,4,5,6
1From 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 ...
2the Department of Epidemiology (D.K.A.), University of Alabama at Birmingham
3the 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
4the Division of Biostatistics (M.A.P.), Washington University School of Medicine, Saint Louis, Mo.
5the Human Genetics Center (J.E.H.), University of Texas, Houston
6the School of Medicine (D.C.), University of Valencia, Spain

Tóm tắt

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.

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Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 27 Số 6

1417-1425

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