on August 26, 2004
Published online before print August 26, 2004, doi: 10.1161/01.ATV.0000143532.93729.d6
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Submitted on July 1, 2004
Accepted on August 18, 2004
ATP-Binding Cassette Transporter G8 Gene As a Determinant of Apolipoprotein B-100 Kinetics in Overweight Men
D. C. Chan ;
From the Lipoprotein Research Unit (D.C.C., G.F.W., P.H.R.B.), School of Medicine and Pharmacology, The Western Australian Institute for Medical Research; and School of Surgery and Pathology (A.J.W., F.M.vB.), University of Western Australia and Department of Biochemistry Royal Perth Hospital, Perth, Australia.
* To whom correspondence should be addressed. E-mail: gfwatts{at}cyllene.uwa.edu.au.
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/m2) 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.
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