Lipoprotein lipase polymorphisms and responses to long-term overfeeding.
OBJECTIVE
The role of the lipoprotein lipase (LPL) gene Hind III, S447X, Bam HI and Pvu II polymorphisms on body composition and lipid and lipoprotein changes in response to long-term overfeeding was studied.


METHODS
Twelve pairs of male monozygotic twins ate a 4.2 MJ day-1 energy surplus, 6 days a week, during a period of 100 days.


RESULTS
Overfeeding induced a decrease in high-density lipoprotein 2 cholesterol (HDL2-C) and HDL2-C to HDL3-C ratio in the H2H2 (n = 12) subjects of the LPL Hind III polymorphism. In contrast, the H1H1/H1H2 (n = 12) subjects experienced increases both in the HDL2-C and HDL2-C to HDL3-C ratio (P = 0.009 and 0.007, respectively, for differences in percentage changes between H2H2 and H1H1/H1H2). In addition, the H2H2 genotype was associated with higher levels of very-low-density lipoprotein triglyceride (VLDL-TG) (P < 0.03) and VLDL-C (P < 0.05) before and after overfeeding and higher HDL-TG levels (P < 0.003) after overfeeding. Postheparin lipoprotein lipase (PH-LPL) activity tended to increase in H1H1/H1H2 and decrease in H2H2 subjects. The H2H2 subjects had lower total HDL-C than those with the genotype H1H1/H1H2 4 months and 5 years after overfeeding (P = 0.04 and 0.10, respectively). The plasma lipid differences were similar amongst subjects with the S447S (n = 4) genotype of the S447X and H2H2 genotype of the Hind III polymorphisms. Body composition changes in response to overfeeding were not different between the Hind III genotypes. LPL Pvu II and Hind III polymorphisms were associated weakly with body weight gain (P = 0.015-0.039) but strongly with adipose tissue LPL activity (P < 0.01) after the caloric surplus.


CONCLUSIONS
We conclude that the H2H2 subjects of the LPL gene Hind III polymorphism experience a decrease in the concentration of antiaterogenic lipoproteins when they are exposed to long-term positive energy balance. This may have been partly caused by a diminished catabolism of TG-rich particles in H2H2 subjects. LPL Pvu II and Bam HI polymorphisms were associated with body weight gain and adipose tissue LPL activity. Genetic variation at the LPL locus could thus be one of the factors responsible for the inter-individual differences observed in plasma lipid and lipoprotein responses to chronic positive energy balance. It must be kept in mind that the sample size for this study was small. Nonetheless, it provides useful information on the genes and pathways that should be further explored.
Ukkola
O
O
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808-4124, USA. bouchac@pbrc.edu
Tremblay
A
A
Bouchard
C
C
D000328:Adult; D001823:Body Composition; D006801:Humans; D006963:Hyperphagia / Q000503:physiopathology*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D008071:Lipoprotein Lipase