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

Abstract

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.