Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study.
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.


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.


CONCLUSIONS
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.
Lai
Chao-Qiang
CQ
Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111, USA. chao.lai@tufts.edu
Arnett
Donna K
DK
Corella
Dolores
D
Straka
Robert J
RJ
Tsai
Michael Y
MY
Peacock
James M
JM
Adiconis
Xian
X
Parnell
Laurence D
LD
Hixson
James E
JE
Province
Michael A
MA
Ordovas
Jose M
JM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D019540:Area Under Curve; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003596:Cytosine; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D006147:Guanine; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D013941:Thymine; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*; D014481:United States
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D014280:Triglycerides; D006147:Guanine; D003596:Cytosine; D013941:Thymine; D011345:Fenofibrate