For example, the APOE locus (encoding Apolipoprotein E which functions in lipoprotein metabolism) has three variants (differing at 2 residues) in the human population (APOE2, -E3, and -E4), each of which has dramatic effects on risk for both late-onset AD (-E4 confers risk) and cardiovascular disease (-E4 also confers risk, as does the rare-E2/-E2 haplotype that also confers risk for hyperlipoproteinemia). This evidence concerns the gene APOE and Alzheimer disease.