Original Article
International Journal of Obesity (2007) 31, 1325–1333; doi:10.1038/sj.ijo.0803586; published online 6 March 2007
Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects
D Brisson1, J St-Pierre2, M Santuré1, T J Hudson3,4, J P Després2,5, M C Vohl6 and D Gaudet1
- 1Department of medicine, Université de Montréal, University of Montreal Community Genomic Medicine Center and Lipid Clinic, Chicoutimi Hospital, Chicoutimi, Canada
- 2Québec Heart Institute, Laval Hospital Research Center, Québec, Canada
- 3McGill University and Genome Quebec Innovation Centre, Montréal, Québec, Canada
- 4Ontario Institute for Cancer Research, Toronto, Ontario, Canada
- 5Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Québec, Canada
- 6Department of Food Sciences and Nutrition and Lipid Research Center, Laval University, Québec, Canada
Correspondence: Dr D Gaudet, Montreal University Community Genomic Medicine Center, Chicoutimi Hospital, 305 St-Vallier, Chicoutimi, Québec, Canada G7H 5H6. E-mail: daniel.gaudet@umontreal.ca
Received 8 June 2006; Revised 21 January 2007; Accepted 26 January 2007; Published online 6 March 2007.
Abstract
Background:
Abdominal obesity and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) increase cardiovascular risk. The very low-density lipoprotein (VLDL) is a triglyceride (TG)-rich particle. Frequent variations in the genes coding for enzymes and proteins involved in the VLDL catabolism have already been documented. The epistatic effect of such variants on the risk profile associated with abdominal obesity remains to be elucidated.
Objective:
This study aims to assess the effect of combinations of frequent single-nucleotide polymorphisms (SNPs) in the VLDL catabolic pathway on the relation between abdominal obesity and fasting TG.
Method:
Only gene variants in the lipoprotein lipase, apolipoprotein (apo) CIII, hepatic lipase and apo E genes known to be frequent in the general population (allele frequency>5%) were included in this study. The presence of selected SNPs was detected by polymerase chain reaction-restriction fragment length polymorphisn in a sample of 640 non-diabetic French Canadians at high cardiovascular risk (405 obese, 235 non-obese).
Results:
Carrying more than two frequent gene variants involved in the VLDL catabolic pathway significantly increased the risk of hyperTG (odds ratio of TG>1.7 mmol/l=4.15; P=0.001). This effect was proportional to the number of SNPs and genes involved and was significantly amplified by the presence of abdominal obesity defined on the basis of waist circumference.
Conclusion:
When combined with abdominal obesity, epistasis in the VLDL pathway has a deleterious effect on fasting TG and coronary artery disease risk profile according to the TG threshold (1.7 mmol/l) used in medical guidelines for the assessment of the metabolic syndrome and associated risk.
Keywords:
hypertriglyceridemia, waist circumference, genetics, epistasis, risk factor
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