Multifunctional metabolic role of apolipoprotein A-II

Abstract

Men with a particular polymorphism of the gene encoding apolipoprotein A-II (apoA-II) have small waist circumference and enhanced metabolism of triglycerides, offering clues to the function of apoA-II.Ferdinand van't Hooft and colleagues investigated the role of apoA-II, a major structural protein of plasma high-density lipoproteins and whose function is largely unknown (Circulation 104, 1223). Scanning the gene's promoter region for a functional polymorphism, the researchers found a common substitution from T to C at position −265 that influences the binding of nuclear proteins. This substitution was associated with significantly lower plasma apoA-II concentration and waist circumference in a sample of 624 healthy 50-year-old men. Furthermore, tests of oral fat tolerance following a meal suggested that subjects homozygous for the −265/C allele had enhanced metabolism of large very low-density lipoproteins.Although it is possible that these observed associations result from functional polymorphisms in other genes, the authors emphasize the similarity between their human data and previous data on mice [Castellani, L.W. et al. (2001) Diabetes 50, 643–651], which strongly suggests that associations between this −265 polymorphism and lipid and fat metabolism relate directly to the gene encoding apoA-II. This would underline the multifunctional metabolic role of the apoA-II protein. HN