期刊
NEUROBIOLOGY OF AGING
卷 27, 期 8, 页码 1087-1093出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2005.05.013
关键词
Alzheimer disease; GSTO1; age-at-onset; association; linkage
资金
- NIA NIH HHS [AG05128, R01 AG021547, R01 AG019757, AG19757, P50 AG005128, U24 AG021886, AG021547] Funding Source: Medline
- NIMH NIH HHS [U01 MH046373, U01 MH046281, U01 MH046290] Funding Source: Medline
- NINDS NIH HHS [R01 NS031153, NS311530] Funding Source: Medline
We previously reported a linkage region on chromosome 10q for age-at-onset (AAO) of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2 (hereafter referred to as GSTOIh) are responsible for the linkage evidence, we identified 39 families in AD that lead to our previous linkage and association findings. The evidence of linkage and association was markedly diminished after removing these 39 families from the analyses, thus providing support that GSTOIh drives the original linkage results. The maximum average AAO delayed by GSTOIh SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/- 4.41) years for AD and 8.6(+/- 5.71) for PD. respectively. This is comparable to the magnitude of AAO difference by APOE-4 in these same AD and PD families. These findings suggest the presence of genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in modifying AAO in these two disorders. (c) 2005 Elsevier Inc. All rights reserved.
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