ATP-binding cassette transporter G8 gene as a determinant of apolipoprotein B-100 kinetics in overweight men

Objective - We examined the influence of genetic variation of the ATP-binding cassette (ABC) transporter G8 on apolipoprotein B ( apoB) kinetics in overweight/obese men. Methods and Results - Very low - density lipoprotein ( VLDL) and low-density lipoprotein (LDL) apoB kinetics were determined in 47 men ( body mass index 32 +/- 3 kg/m(2)) using stable isotope and multicompartmental modeling to estimate production rate ( PR), fractional catabolic rate (FCR), and VLDL to LDL - apoB conversion. Relative to the wild-type (400TT), subjects carrying the ABCG8 400K allele had significantly decreased plasma concentrations of triglycerides, sitosterol, and campesterol, lower PR of VLDL - apoB, and higher VLDL to LDL - apoB conversion ( P < 0.05). The PR and FCR of LDL - apoB were also significantly higher with 400K allele ( P < 0.05). No association was found with ABCG8 D19H. Compared with APOE2 or APOE3, APOE4 carriers had significantly higher plasma LDL-cholesterol concentrations and lower LDL - apoB FCR. During multiple regression analysis including age, homeostasis model assessment score, plasma concentrations of sitosterol, and lathosterol, ABCG8 and apoE genotypes were independent determinants of VLDL - apoB PR and LDL - apoB FCR, respectively ( P < 0.05). Conclusions - Variation in the ABC transporter G8 appears to independently influence the metabolism of apoB-containing lipoproteins in overweight/obese subjects. This may have therapeutic implications for the management of dyslipidemia in these subjects.