Gs216

Gs216
Magnitude	6
Repute	Bad
Summary	2 copies of the APOE-ε4 allele
Criteria	Gs216/criteria

Possessing two copies of the ApoE-ε4 allele confers a greater risk for all the diseases to 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.

Alzheimer's disease

Caucasians with two copies of the APOE-ε4 allele are part of the ~1.7% of the population who are ~11x times more likely than average to develop Alzheimer's disease. Wired magazine.

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]

A 2017 publication states a lifetime risk of Alzheimer's for ApoE4/ApoE4 individuals of 31 - 40%; and through observation (not modelling), they reported a five-year risk for APOE E4/E4 individuals ranging from 0 - 23% in those entering the study at age 60 to 64 years; 9 - 35% in those entering at 65 to 69 years; and 19 - 38% in those entering at 70 to 75 years.[PMID 28940650]

[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."

Cardiovascular disease

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.

Hepatitis C

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].

Community

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

Clinical Trials

The Generation Program is made up of two clinical trials: Generation Study 1 and Generation Study 2. These studies will test medications that may prevent Alzheimer’s. Each trial will last for 5 – 8 years and will be investigating products, which aim to prevent the onset of the disease. To qualify for the Generation Program, you need to meet the following requirements:

• 60 to 75 years of age
• Normal memory and thinking ability
• 1 or 2 copies of the APOE ε4 allele
• Have a study partner willing to attend necessary study visits

Find out more about becoming a candidate at GenerationProgram.com or by calling 1-866- 244-8907.

Genoset gs141 identifies carriers of a single ApoE-ε4 allele.