Genetic variation in the microsomal triglyceride transfer protein (MTP) affects the secretion pattern and plasma concentration of apolipoprotein (aopB)-containing lipoproteins and a common functional -493 G/T polymorphism has been reported to influence plasma lipids levels. Recent data suggest that carriers of the T allele might be more sensitive to detrimental factors such as features of the insulin resistance syndrome. Since type 2 diabetes is associated with obesity and insulin resistance, the present study investigated the effect of this polymorphism on plasma lipids, apoB and LDL subfractions in 281 Chinese type 2 diabetic subjects and 364 non-diabetic controls. The frequency of the rare T allele was 0.162 and 0.126 in subjects with and without diabetes respectively. There were no differences in the effect of the polymorphism on plasma lipids and apoB in the two groups. However, the TT genotype was associated with a higher concentration of small dense LDL-III than the GT or GG variants in the diabetic subjects (P=0.01) whereas no such effect was observed in the controls. In the diabetic patients, age, plasma triglyceride and the MTP genotype were independent determinants of LDL-III concentrations in linear regression analysis (R(2)=10%, P=0.04) whereas in the controls, only plasma triglyceride and age were important determinants (R(2)=15%, P=0.01). In conclusion, the -493 G/T polymorphism only has a minor effect on LDL subfraction pattern in Chinese and the effect is only apparent in the presence of type 2 diabetes.