Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects

• Published in: International Journal of Obesity Vol. 31; no. 8; pp. 1325 - 1333
• Main Authors: Brisson, D, St-Pierre, J, Santure, M, Hudson, T.J, Despres, J.P, Vohl, M.C, Gaudet, D
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.08.2007; Nature Publishing Group
• Subjects: abdominal fat; Apolipoprotein C-III - genetics; Apolipoprotein C-III - metabolism; Apolipoprotein E2 - genetics; Apolipoprotein E2 - metabolism; Apolipoprotein E4 - genetics; Apolipoprotein E4 - metabolism; biochemical pathways; Biological and medical sciences; Canada; Canadians; cardiovascular diseases; Complications and side effects; Coronary heart disease; coronary vessels; Disorders of blood lipids. Hyperlipoproteinemia; epidemiological studies; epistasis; Epistasis, Genetic; etiology; Feeding. Feeding behavior; Female; France - ethnology; Fundamental and applied biological sciences. Psychology; gene frequency; Genetic aspects; Health aspects; human genetics; Humans; hypertriglyceridemia; Hypertriglyceridemia - ethnology; Hypertriglyceridemia - genetics; Hypertriglyceridemia - metabolism; Lipase - genetics; Lipase - metabolism; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Lipoproteins, VLDL - metabolism; Low density lipoproteins; Male; Medical sciences; Metabolic diseases; metabolic syndrome; Middle Aged; molecular genetics; molecular sequence data; nucleotide sequences; Obesity; Obesity - ethnology; Obesity - genetics; Obesity - metabolism; Phenotype; phenotypic variation; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR gamma - genetics; PPAR gamma - metabolism; Risk factors; single nucleotide polymorphism; triacylglycerols; Triglycerides - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; very low density lipoprotein; waist circumference; Waist-Hip Ratio; Canada; France; Human; Obesity; Lipoprotein VLDL; Nutrition; Anthropometry; Nutrition disorder; Variations; Lipids; Metabolic diseases; Corporal biometry; Hyperlipoproteinemia; Epistasis; Triglyceride; Enzymopathy; Epidemiology; Waist circumference; Association; Hypertriglyceridemia; Risk factor; Genetics; Dyslipemia; Nutritional status; Triglyceridemia
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803586

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.