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.


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.
Chan
D C
DC
Lipoprotein Research Unit, School of Medicine and Pharmacology, The Western Australian Institute for Medical Research, Perth, Western Australia.
Watts
G F
GF
Barrett
P H R
PH
Whitfield
A J
AJ
van Bockxmeer
F M
FM
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B