rs429358

This SNP, located in the fourth exon of the ApoE gene, affects the amino acid at position 130 of the resulting protein. The more common rs429358 allele is (T). If the allele 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. 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). Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it. {{PMID Auto GWAS |PMID=21123754 |Trait=None |Title=Genome-wide association study of CSF biomarkers A{beta}1-42, t-tau, and p-tau181p in the ADNI cohort. |RiskAllele= |Pval=0.000001 |OR=None |ORtxt=None |OA=1 }}

C;C

One of 2 snps which is necessary to identify ApoE4. rs429358(C;C) individuals have an increased risk of developing Alzheimer's disease PMID 15956169. APOE4 differences only affect the brain after age 60. The memory changes that occur from 20 to 60 do not seem to be connected to APOE4 at all. today.reuters.com eurekalert.org Patients with Alzheimer's disease who have at least one ApoE4 allele were found to benefit from a therapy that was ineffective in those who lacked medscape.com Inheritance of the rs1799724(T) allele (a variant in another gene, TNF) appears to synergistically increase the risk of Alzheimer's in APOE4 carriers and is associated with altered CSF Abeta42 levels PMID 15895461 PMID 17192785 The researchers found that on testing DNA samples from 1,086 well-characterized Alzheimer's disease cases, a single SNP (rs4420638) lying 14 kb distal to the ApoE locus has a powerful association with late-onset AD (corrected p value was 5.3 x 10 e-34). No other SNP showed as robust an association. The authors estimated that people with two ApoE4 copies, such as a person with the rs429358(C;C) genotype, have a 25-fold increased risk for developing the disease compared to ApoE3/ApoE3 carriers. alzforum.org