Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family.

Proc Natl Acad Sci U S A 2004 Nov 26;101(44):15688-93. Epub 2004 Oct 26.

Celera Diagnostics, Alameda, CA 94502, USA.

Although several genes have been implicated in the development of the early-onset autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene. Subsequent analysis of GAPD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the casecontrol series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.0403535101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC524264PMC
November 2004
16 Reads

Publication Analysis

Top Keywords

disease risk
8
gapd gene
8
alzheimer's disease
8
gapd genes
8
gapd
6
association
5
disease
5
series suggesting
4
variants functionally
4
series totaling
4
subjects report
4
totaling 1089
4
load patients
4
1196 control
4
control subjects
4
suggesting variants
4
patients 1196
4
functionally genes
4
1089 load
4
chromosome multiple
4

References

(Supplied by CrossRef)

Myers et al.
Current opinion in neurology 2001

Tanzi et al.
Neuron 2001

Kennedy et al.
Science 2003

Hardy et al.
Science 2002

Selkoe et al.
Science 2002

ROSES et al.
Annals of the New York Academy of Sciences 1998

Warwick Daw et al.
American journal of human genetics 2000

Human Molecular Genetics 1999

Blacker et al.
Human Molecular Genetics 2003

Myers et al.
Science 2000

Myers et al.
American journal of medical genetics 2002

Similar Publications