Human evidence that the apolipoprotein A-II gene is implicated in visceralfat accumulation and metabolism of triglyceride-rich lipoproteins

Background-Apolipoprotein (apo) A-II is a major structural protein of plasm a HDLs, but little is known regarding its functions. Methods and Results-To investigate the physiological role of apoA-II in hum ans, we screened the promoter region of the apoA-II gene for a functional p olymorphism 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 mobilit y shift assays demonstrated that the -265T/C polymorphism influences the bi nding of nuclear proteins, whereas transient transfection studies in human hepatoma cells showed a reduced basal rate of transcription of the -265C al lele compared with the -265T allele. The -265C allele was associated with d ecreased plasma apoA-II concentration and decreased waist circumference in healthy 50-year-old men. In addition, oral fat tolerance tests provided evi dence 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.