期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 44, 页码 15688-15693出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0403535101
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资金
- NIA NIH HHS [P01 AG 03991, U24 AG021886, P01 AG003991, P50 AG005131, P50 AG 05681, P50 AG005681, R01 AG 16208, R01 AG016208, P50 AG 05131] Funding Source: Medline
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 case-control 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.
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