Regulatory gene mutations affecting apolipoprotein gene expression: functions and regulatory behavior of known genes may guide future pharmacogenomic approaches to therapy.

摘要: A pharmacogenomic approach to therapy requires systematic knowledge of the regulatory regions genes, as well basic understanding transcriptional mechanisms genes. Using apolipoprotein (apo) A-I/CIII gene cluster a model system, we have identified by in vitro and vivo studies elements factors which control its transcription. Studies transgenic mice established that hepatocyte nuclear factor (HNF-4) binding site apoCIII enhancer, controls transcription both is required for intestinal expression apoA-I enhances synergistically their hepatic vivo. The three Sp1 sites enhancer are also apoA-land apoC-III genes vivo, enhancement regulation apoE/apoCl/ apoCIV/apoCII cited. It expected identification will be soon accelerated sequencing several mammalian genomes. functional analyses domains involved lipid homeostasis, combined with cross-species sequence comparisons near future, may identify natural polymorphisms general population permit rational approaches treatment dyslipidemias.