Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants: The GOLDN Study

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 27; no. 6; pp. 1417 - 1425
• Main Authors: Lai, Chao-Qiang, Arnett, Donna K., Corella, Dolores, Straka, Robert J., Tsai, Michael Y., Peacock, James M., Adiconis, Xian, Parnell, Laurence D., Hixson, James E., Province, Michael A., Ordovas, Jose M.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.06.2007; Hagerstown, MD Lippincott
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Apolipoprotein A-V; Apolipoproteins A - genetics; Area Under Curve; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Cytosine; Dietary Fats - administration & dosage; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fenofibrate - administration & dosage; Fenofibrate - therapeutic use; Gene Frequency; General and cellular metabolism. Vitamins; Genotype; Guanine; Humans; Hyperlipidemias - drug therapy; Hyperlipidemias - genetics; Hyperlipidemias - metabolism; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - therapeutic use; Lipid Metabolism - drug effects; Male; Medical sciences; Middle Aged; Particle Size; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide; Postprandial Period; Thymine; Time Factors; Treatment Outcome; Triglycerides - blood; United States; Vasodilator agents. Cerebral vasodilators; gene-drug interaction; Fibrate derivatives; Postprandial; Lipids; Cardiovascular disease; Apolipoprotein; Triglyceride; APOA5; Vascular disease; Fenofibrate; Atherosclerosis; triglyceride lowering; Drug interaction; Lipoprotein HDL; increasing HDL-C; Antilipemic agent
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.107.140103

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.