rs1129844

rs1129844, also known as c.208G>A, p.Ala23Thr and A23T, is a SNP in the CCL11 gene on chromosome 17. The CCL11 gene encodes eotaxin-1, a chemokine protein who's serum and cerebrospinal fluid levels increase with age and may correlate with decreased neurogenesis. This SNP has made the news based on a (single) study reporting that carriers of an rs1129844(A) allele might have delayed onset of Alzheimer's disease compared to individuals lacking an (A) allele. An analysis of 72 whole genome scans of selected Colombian PSEN1 E280A carriers, i.e. rs63750231(A;C) genotypes, all of whom have early-onset Alzheimer's, found that a protective haplotype delayed Alzheimer disease onset by up to 10 years. The only coding SNP in this protective haplotype associated with delayed AD onset was rs1129844. A follow-on study in 152 Alzheimer patients in a UCSF cohort (average onset age 63 years, which is considered late-onset and is the more common type of Alzheimer's) did not find a statistically significant protective effect for the rs1129844(A) allele, but did observe a "trend" towards protection in the data. The (A) allele has a frequency of about 16% in most populations (ExAC), although the study suggests that 1 in 4 individuals may carry this allele. A news brief about this is here. An analysis of 117 whole genome scans of Colombian E280A PS1 carriers found that a protective haplotype delayed Alzheimer disease onset by 10 years. These E280A carriers are certain to develop dementia. The only SNP within a coding region of a gene in this protective haplotype associated with delayed AD onset was rs1129844, The protective haplotype occurred in 1 in 4 carriers; the A allele also occurs with a frequency of approximately 25%. A follow-on study confirmed the protection of rs1129844 in 152 AD patients. http://www.alzforum.org/news/conference-coverage/new-genetics-frontiers-finding-modifiers-making-sense-pathways

A;A

One publication reports that the (A;G) genotype of rs1129844 might delay by up to 10 years early-onset Alzheimer's disease caused by a mutation in the PSEN1 gene. It is not clear whether an Alzheimer's risk benefit might result from the (A;A) genotype. See additional discussion at rs1129844, and the citation to the study in which Supplementary Figure 5 shows a statistically nonsignificant, although positive, trend towards delayed onset of dementia in a UCSF patient cohort of late-onset Alzheimer's patients carrying the (A;A) rs1129844 genotype. This should be viewed cautiously until confirmed in larger Alzheimer's populations.

A;G

One publication reports that the (A;G) genotype of rs1129844 might significantly delay the onset of early-onset Alzheimer's disease caused by a mutation in the PSEN1 gene. A followup study in late-onset Alzheimer patients found a 2.5 year later onset in those with AG versus GG genotype, but it was not statistically significant. This is an initial report and will need further replications. See additional discussion at rs1129844.