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.
Lipoprotein Research Unit, School of Medicine and Pharmacology, The Western Australian Institute for Medical Research, Perth, Western Australia.
D C
DC
Chan
G F
GF
Watts
P H R
PH
Barrett
A J
AJ
Whitfield
F M
FM
van Bockxmeer
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