Effect of apoC-III gene polymorphisms on the lipoprotein-lipid profile of viscerally obese men.
Abdominal visceral adipose tissue (AT) accumulation is associated with an atherogenic metabolic profile that includes increased plasma triglyceride (TG), low HDL cholesterol levels, and an insulin-resistant hyperinsulinemic state. Whereas the apolipoprotein (apo) C-III C3238G gene variant, often referred to as the SstI polymorphism, has been related to variations in plasma TG concentrations, another variation within the insulin responsive element (C-482T) of the apoC-III gene has been associated with greater glucose and insulin responses to an oral glucose tolerance test (OGTT); however, these results were obtained in nonobese individuals. We therefore investigated the effects of three apoC-III gene polymorphisms, namely SstI, C-482T, and T-455C, on fasting plasma lipoprotein-lipid levels and response to a 75 g OGTT in a sample of 122 viscerally obese men (abdominal visceral AT area >or=130 cm(2)). Among the three gene variants that were examined, the SstI variation was the only one found to be associated with hypertriglyceridemia. Indeed, S1/S2 heterozygotes (n = 24) were characterized by increased fasting plasma TG concentrations compared with S1/S1 homozygotes (n = 98) (mean +/- SD: 3.03 +/- 1.58 vs. 2.34 +/- 0.95 mmol/l respectively, P < 0.05). The higher TG concentrations in S1/S2 were associated with the presence of smaller, denser LDL particles compared with S1/S1 subjects (LDL peak particle diameter: 24.8 +/- 0.5 nm vs. 25.1 +/- 0.5 nm respectively, P < 0.05). Furthermore, there was no association between the response to the OGTT and any of the apoC-III gene variants (SstI, T-455C, or C-482T) examined. Results of the present study support the notion of a hypertriglyceridemic effect associated with the apoC-III SstI polymorphism that could modulate the magnitude of the dyslipidemic state in abdominally obese patients.
Couillard
Charles
C
Department of Food Sciences and Nutrition, Laval University, Sainte-Foy, Québec, Canada, G1K 7P4.
Vohl
Marie-Claude
MC
Engert
James C
JC
Lemieux
Isabelle
I
Houde
Alain
A
Almeras
Natalie
N
Prud'homme
Denis
D
Nadeau
Andre
A
Despres
Jean-Pierre
JP
Bergeron
Jean
J
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000483:Alleles; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005215:Fasting / Q000097:blood; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D014781:Viscera
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D014280:Triglycerides