期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 131, 期 2, 页码 105-110出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2009.12.007
关键词
Alzheimer's disease; Cataract; NFE2L2; Nrf2; KEAP1; Oxidative stress
资金
- Swedish Research Council
- Alzheimer's Association [NIRG-08-90356]
- cNEUPRO
- Royal Swedish Academy of Sciences
- Sahlgrenska University Hospital
- West Sweden RUN
- Edith Jacobsson Foundation
- Axel Linders Foundation
- Goteborg Medical Society
- Swedish Medical Society
- Swedish Brain Power
- Stiftelsen for Gamla Tjanarinnor
- Gun och Bertil Stohnes stiftelse
- Kronprinsessan Margaretas Arbetsnamnd for Synskadade
- Handlanden Hjalmar Svensson Foundation
- Ahlen Foundation
- Magn. Bergvall's Foundation
- Alzheimer Foundation, Sweden
Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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