TY - JOUR
T1 - Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants
T2 - The GOLDN study
AU - Lai, Chao Qiang
AU - Arnett, Donna K.
AU - Corella, Dolores
AU - Straka, Robert J.
AU - Tsai, Michael Y.
AU - Peacock, James M.
AU - Adiconis, Xian
AU - Parnell, Laurence D.
AU - Hixson, James E.
AU - Province, Michael A.
AU - Ordovas, Jose M.
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
KW - APOA5
KW - Fenofibrate
KW - Gene-drug interaction
KW - Increasing HDL-C
KW - Triglyceride lowering
UR - http://www.scopus.com/inward/record.url?scp=34249294501&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.107.140103
DO - 10.1161/ATVBAHA.107.140103
M3 - Article
C2 - 17431185
AN - SCOPUS:34249294501
SN - 1079-5642
VL - 27
SP - 1417
EP - 1425
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 6
ER -