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The FAS gene, brain volume, and disease progression in Alzheimer's disease
Author(s) -
ErtenLyons Deniz,
Jacobson Anne,
Kramer Patricia,
Grupe Andrew,
Kaye Jeffrey
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.663
Subject(s) - single nucleotide polymorphism , brain size , minor allele frequency , oncology , snp , proportional hazards model , medicine , allele , disease , magnetic resonance imaging , dementia , bioinformatics , genotype , gene , biology , genetics , radiology
Objective We sought to identify single‐nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) progression and brain volume. Methods Ninety‐seven SNPs were genotyped in 243 subjects from a longitudinal study of healthy aging. Subjects who received a diagnosis of cognitive impairment (CI) at any study visit (before their most recent visit) and had DNA in the study's DNA bank were included. Progression of AD was defined as the duration from onset of CI to diagnosis of AD. Association of each of the 97 SNPs with AD progression was tested via Cox model. Those SNPs meeting a criterion of nominal significance ( P < 0.05) for association with AD progression were reassessed to account for multiple testing by repeating the marker selection process in 10,000 random permutations. Next, the association between the one SNP that survived the multiple‐testing adjustment and brain volume was determined by multiple regression analysis in a subgroup of subjects for whom magnetic‐resonance imaging (MRI)‐derived brain‐volume data were available. Brain volumes were adjusted for age at MRI, gender, and time from MRI to onset of CI. Results The minor allele of rs1468063 in the FAS gene, which is member 6 of the tumor necrosis factor receptor superfamily, was significantly associated with faster AD progression after adjustment for multiple testing ( P permutation = 0.049). The same allele in rs1468063 was associated with smaller brain volumes and larger ventricular volumes ( P = 0.02 and 0.04, respectively). Conclusions The FAS gene, which plays a role in apoptosis, may be associated with AD by modulating the apoptosis and neuronal loss secondary to AD neuropathology.