The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males during the consumption of diets with different fat content.

Several apo B polymorphic sites have been studied for their potential use as markers for CHD in the population and for potential gene-diet interactions. Our aim was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies insulin sensitivity to dietary fat. We studied fifty-nine healthy volunteers (thirty men and twenty-nine women, thirty-six homozygotes for the -516C allele (C/C) (nineteen males and seventeen females) and twenty-three heterozygotes for the -516T allele (C/T) (eleven males and twelve females)). Subjects consumed three diets during the feeding study, 4 weeks each: an SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate (CHO)-rich diet (30 % fat, 55 % CHO) or a MUFA-rich diet (38 % fat, 22 % MUFA) following a randomised cross-over design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. Male carriers of the -516T allele showed a significantly greater decrease in steady-state plasma glucose concentrations when changing from the SFA-rich diet (9.18 (sd 1.35) mmol/l) to the MUFA (6.55 (sd 0.74) mmol/l) or the CHO (6.31 (sd 0.93) mmol/l) diets than did those who were homozygous for the C allele (P = 0.040). Furthermore, C/T subjects presented higher plasma NEFA values after consumption of the SFA diet compared with the MUFA and CHO diets (P = 0.001). This effect was not observed in females (P = 0.908). Our findings show that male carriers of the -516T allele, C/T, have a significant increase in insulin resistance after consumption of all diets, but the difference is more exaggerated after the SFA diet compared with the MUFA- and CHO-rich diets.