To the Editor: In overweight subjects, an elevated supply of intracellular lipid stimulates the microsomal triglyceride transfer protein (MTP)- dependent assembly of apoB-containing lipoproteins in both intestinal and hepatic tissues, with subsequent secretion into the circulation. The severity of the dyslipidemia which results is however highly variable among overweight subjects, suggesting that genetic background may modulate the dyslipidemic effect of excess weight. In this context, a functional polymorphism in the MTP gene promoter region was recently described in which homozygotes for a G-to-T substitution, located 493 bp upstream from the transcription initiation site, display lower plasma levels of apoB-containing lipoproteins than carriers of the 493G allele. Hypothetically, such a functional polymorphism of the MTP promoter may attenuate the dyslipidemic effects of excess body weight and, in this way, equally attenuate the development of athero- sclerotic disease in overweight subjects. We evaluated this hypothesis in 326 normotensive nondiabetic subjects with a broad range of body mass indices (BMI; 16.6 to 40.0kg/m 2 ) who were consecutively evaluated at the Endocrinology Department of La Pitie ´-Salpetriere Hospital in Paris, France and were considered to be at low cardiovascular risk (n189) or were enrolled as healthy volunteers in the Stanislas Cohort, Nancy, France (n137). The MTP 493G/T promoter genotype was deter- mined as described by Karpe et al.1 Plasma levels of total cholesterol and triglycerides were determined by nephelometry, and HDL-choles- terol concentration was determined enzymatically with a commercially available kit (Biomerieux). Ultrasonographic evaluation of the extracra- nial carotid arteries was performed with a duplex system (ACUSON Sequoia 512). The sum of the intima media thickness (IMT) of the right and left carotid artery walls was determined as an index of global carotid disease. Genotype frequencies behaved within the limits of the Hardy Wein- berg law and were similar to those reported in previous studies. There was no significant difference in age (479, 469, and 469 years), BMI (24.73.6, 24.34.3, and 23.22.9 kg/m 2