|Summary||2 copies of the APOE-ε4 allele|
Possessing two copies of the ApoE-ε4 allele confers a much greater risk of all the diseases for which an individual with just one allele is at risk: an increased risk of Alzheimer's disease, other types of dementia, and cardiovascular disease (heart disease). The APOE-ε4 allele is protective against Hepatitis C-induced liver damage [PMID 20109174], and possibly vitamin D deficiency, and seems to confer a survival advantage to children with severe diarrhea. Possessing two copies is thought to confer even greater protection.
Individuals of European descent's risk of Alzheimer's is about 45% (for developing the disease by age 80), with an adjusted odds ratio of about 11x. Another estimate puts the remaining lifetime risk for this genotype at age 65 for developing Alzheimer's at 35% for males and 53% for females.[PMID 11136203]
[PMID 9508150] "The presence of an APOE-epsilon4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype. These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics."
Meta-analyses indicate that individuals homozygous for ApoE-ε4 are at 40-50% increased risk for cardiovascular disease [PMID 17466101]. This risk is attributed generally to 5-10% higher total cholesterol, LDL cholesterol, and triglyceride levels [PMID 17466101], although other mechanisms cannot be ruled out.
In 420 Caucasian individuals exposed to Hepatitis C, those with the APOE-ε4 allele showed reduced likelihood of chronic infection with an odds ratio of 0.6 (95% CI 0.38-0.96), p = 0.032 [PMID 16299033]. Additionally, the ApoE-ε4 allele is protective against Hepatitis C-induced severe liver inflammation and fibrosis [PMID 12143056].
Learning while you are healthy that your odds of developing Alzheimer's may be as high as 50% by the time you are 80 years old can be a shock. Some of the people who have learned about their higher risk have formed ApoE4.info, a non-profit for ApoE4 carriers to discuss research and provide support. This includes a research wiki and a discussion forum.
Additional online resources include:
- A reddit discussion on this topic
- The Alzheimer's Association, focusing primarily on those diagnosed with the disease and their caregivers in addition to promoting research & treatment
Genoset gs141 identifies carriers of a single ApoE-ε4 allele.