The C (minor) allele is associated with:
- rs429358(C;C) + rs7412 (C;C) = APOE4/APOE4 (Bad) = 12x for late-onset Alzheimer's and 61x for early-onset disease [R].
- rs429358(C;T) + rs7412 (C;C) = APOE4/APOE3 (Bad) = >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease [R].
- rs429358(T;T) + rs7412 (C;C) = APOE3/APOE3 (Good)
If the allele of this SNP is "C" and the same chromosome also harbors the rs7412 "C" allele, the combination is known as an APOE-ε4 allele. The APOE-ε4 allele has a strong influence on the risk of Alzheimer's disease.
Many studies have estimated the level of risk, and it varies depending on age, sex, ethnicity, and other factors. One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease [R].
Meta-analyses have also supported the association between the APOE-ε4 allele and somewhat increased risk for heart disease, with an odds ratio of 1.42 (CI: 1.26 - 1.61) [R].