Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

J Clin Endocrinol Metab. 2007 Jun;92(6):2280-5. doi: 10.1210/jc.2006-1802. Epub 2007 Mar 13.

Abstract

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.

Design and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Apolipoprotein A-V
  • Apolipoprotein B-100 / genetics
  • Apolipoprotein B-100 / metabolism
  • Apolipoprotein B-48 / genetics
  • Apolipoprotein B-48 / metabolism
  • Apolipoproteins A / genetics*
  • Apolipoproteins A / metabolism*
  • Coronary Disease / ethnology
  • Coronary Disease / genetics
  • Energy Metabolism / genetics*
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Lipoproteins / metabolism*
  • Male
  • Polymorphism, Single Nucleotide
  • Postprandial Period / physiology*
  • Risk Factors
  • Triglycerides / blood
  • White People / genetics

Substances

  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoprotein B-100
  • Apolipoprotein B-48
  • Apolipoproteins A
  • Lipoproteins
  • Triglycerides