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(Circulation. 2001;104:1223.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Human Evidence That the Apolipoprotein A-II Gene Is Implicated in Visceral Fat Accumulation and Metabolism of Triglyceride-Rich Lipoproteins

Ferdinand M. van ’t Hooft, MD, PhD; Giacomo Ruotolo, MD, PhD; Susanna Boquist, MD, PhD; Ulf de Faire, MD, PhD; Gösta Eggertsen, MD, PhD; Anders Hamsten, MD, PhD

From the Atherosclerosis Research Unit (F.M.v.H., G.R., S.B., A.H.), Department of Medicine, Karolinska Hospital; the Division of Cardiovascular Epidemiology (U. de F.), Institute of Environmental Medicine; and the Division of Clinical Chemistry (G.E.), Department of Laboratory Sciences, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.

Correspondence and reprints requests to Dr Ferdinand M. van ’t Hooft, King Gustaf V Research Institute, Karolinska Hospital, S-17176 Stockholm, Sweden. E-mail Ferdinand.vant.Hooft{at}medks.ki.se

Background— Apolipoprotein (apo) A-II is a major structural protein of plasma HDLs, but little is known regarding its functions.

Methods and 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.

Key Words: lipoproteins • apolipoproteins • metabolism • genetics • obesity

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