Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population.
BACKGROUND
Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, and c.1259T>C) in the APOA5 gene define three common haplotypes (APOA5*1, APOA5*2, and APOA5*3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males.


METHODS
Eighty-eight APO E3/3 volunteers [67 with (-1131T and 56C) APOA5*1 haplotype, 12 with (-1131C and 56C) APOA5*2 haplotype, and nine with (-1131T and 56G) APOA5*3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined.


RESULTS
Subjects with the APOA5*2 and APOA5*3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5*1 haplotype.


CONCLUSIONS
Our findings show that the presence of the APOA5*2 and APOA5*3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and -1131C alleles.
Moreno-Luna
Rafael
R
Unit of Lipids and Atherosclerosis, Hospital Universitario Reina Sofía, Avda Menéndez Pidal, Córdoba, Spain.
Perez-Jimenez
Francisco
F
Marin
Carmen
C
Perez-Martinez
Pablo
P
Gomez
Purificacion
P
Jimenez-Gomez
Yolanda
Y
Delgado-Lista
Javier
J
Moreno
Juan A
JA
Tanaka
Toshiko
T
Ordovas
Jose M
JM
Lopez-Miranda
Jose
J
D000328:Adult; D000072040:Apolipoprotein A-V; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism; D053283:Apolipoprotein B-48 / Q000235:genetics / Q000378:metabolism; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism*; D003327:Coronary Disease / Q000208:ethnology / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period / Q000502:physiology*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001054:Apolipoproteins A; D008074:Lipoproteins; D014280:Triglycerides