Human evidence that the apolipoprotein a-II gene is implicated in visceral fat accumulation and metabolism of triglyceride-rich lipoproteins.
BACKGROUND
Apolipoprotein (apo) A-II is a major structural protein of plasma HDLs, but little is known regarding its functions.


RESULTS
To investigate the physiological role of apoA-II in humans, we screened the promoter region of the apoA-II gene for a functional polymorphism and used this polymorphism as a tool in association studies. A common, functional polymorphism in the promoter region of the apoA-II gene, a T to C substitution at position -265, was found. Electrophoretic mobility shift assays demonstrated that the -265T/C polymorphism influences the binding of nuclear proteins, whereas transient transfection studies in human hepatoma cells showed a reduced basal rate of transcription of the -265C allele compared with the -265T allele. The -265C allele was associated with decreased plasma apoA-II concentration and decreased waist circumference in healthy 50-year-old men. In addition, oral fat tolerance tests provided evidence that the -265C allele enhances postprandial metabolism of large VLDLs.


CONCLUSIONS
ApoA-II appears to promote visceral fat accumulation and impair metabolism of large VLDLs.
van 't Hooft
F M
FM
Atherosclerosis Research Unit, Department of Medicine, Karolinska Hospital, Sweden. Ferdinand.vant.Hooft@medks.ki.se
Ruotolo
G
G
Boquist
S
S
de Faire
U
U
Eggertsen
G
G
Hamsten
A
A
D000273:Adipose Tissue / Q000378:metabolism*; D000483:Alleles; D026923:Amino Acid Transport Systems, Basic; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D001824:Body Constitution / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D026923:Amino Acid Transport Systems, Basic; D016633:Apolipoprotein A-II; D002352:Carrier Proteins; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014280:Triglycerides; D004247:DNA