Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein -493G/T polymorphism on plasma lipoprotein levels in men.
The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) -493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP -493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP -493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein--lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm(2)) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein--lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP -493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter.
St-Pierre
Julie
J
Dyslipidemia, Diabetes and Atherosclerosis Group, Complexe Hospitalier de la Sagamie, Chicoutimi Que., Canada G7H 5H6.
Lemieux
Isabelle
I
Miller-Felix
Isabelle
I
Prud'homme
Denis
D
Bergeron
Jean
J
Gaudet
Daniel
D
Nadeau
Andre
A
Despres
Jean Pierre
JP
Vohl
Marie Claude
MC
D000005:Abdomen / Q000473:pathology*; D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome; D008861:Microsomes / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
D001055:Apolipoproteins B; D002352:Carrier Proteins; D008055:Lipids; D008074:Lipoproteins; C106092:microsomal triglyceride transfer protein