Regulatory mutations in human lipoprotein disorders and atherosclerosis.

Most known mutations underlying human lipoprotein abnormalities affect the protein coding sequence of the gene involved. Mutations in the regulatory regions-promoters, enhancers, binding sites for transcription factors and other elements-may markedly alter the transcription efficiency of lipid-regulatory genes, and may thus cause an inherited defect of lipoprotein metabolism. Reported examples include mutations of the promoters of the human LDL and lipoprotein lipase genes. Common variation of the DNA sequence in the promoter region, such as that occurring in the human apolipoprotein A-I and plasminogen activator inhibitor(-1) genes, may account for subtle differences in serum lipid levels and risk of atherosclerotic vascular disease in the general population.