APOE Genotype Risk Index (E2/E3/E4 variants): Explanation and Clinical Context The Apolipoprotein E (APOE) gene has three major alleles: E2, E3, and E4. The combination of these alleles determines an individual's genotype, which significantly influences lifetime risk for Alzheimer's disease and cardiovascular outcomes.
E2 allele is generally protective, E3 is neutral, and E4 increases risk, particularly in homozygous E4/E4 carriers.
Relative risk index quantifies the increased or decreased risk of Alzheimer's disease compared to the E3/E3 genotype, which serves as the reference (risk = 1.0).
This tool allows clinicians and researchers to quickly estimate genotype-associated risk for cognitive decline, aiding in preventive strategy discussions and patient counseling.
Reference:
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921-923. doi:10.1126/science.8346443
Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. JAMA. 1997;278:1349-1356. doi:10.1001/jama.278.16.1349