Geno
|
Mag
|
Summary
|
(C;C)
|
1
|
Faster progression of mild cognitive impairment to Alzheimer’s disease.
|
(C;T)
|
1
|
Normal progression to Alzheimer’s disease from mild cognitive impairment.
|
(T;T)
|
1
|
Normal progression to Alzheimer’s disease from mild cognitive impairment.
|
rs12752888 is a SNP on chromosome 1 upstream of the gene ACOT11. ACOT11 has been associated with obesity and is a member of a family of enzymes that help catalyze the de-esterification of fatty acids.
One study used genotyping information from 489 patients with mild cognitive impairment (MCI) from the Vitamin E trial. The GWAS employed used Alzheimer’s disease progression measured quantitatively from Clinical Dementia Rating-sum of boxes (CRD-SB) scores over time. Additionally, the study utilized information about 200 Alzheimer’s disease patients, 300 MCI patients, and 200 controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) consortium. Significance was assessed based on the interaction term between genotype and time in a Cox proportional hazards model. rs12752888 was among two SNPs in the GWAS study to reach genome-wide significance in the Vitamin E MCL trial with a false-positive rate of 0.05 adjusting for 1 million SNPs (p < 8.31 × 10^−9 ). Combining both datasets, rs12752888 reached significance of p = 3.08 x 10^-11. Overall with a hazard rate of 1.78, this suggests that the homozygous recessive genotype contributes to a faster rate of cognitive decline in mild cognitive impaired individuals in their progression to Alzheimer’s disease. [PMID 3309471]