|(A;A)||2.5||Up to 10 year delay in onset of early-onset Alzheimer's (possibly)|
|(A;G)||2||Significant delay in onset of early-onset Alzheimer's; possibly a 2.5 year delay in onset of late-onset Alzheimer's|
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.[PMID 21886162]
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.[PMID 26324103] A news brief about this is here.
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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