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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract

von Otter, Malin; Landgren, Sara; Nilsson, Staffan; Zetterberg, Madeleine; Celojevic, Dragana; Bergstrom, Petra; Minthon, Lennart LU ; Bogdanovic, Nenad; Andreasen, Niels and Gustafson, Deborah R., et al. (2010) In Mechanisms of Ageing and Development 131(2). p.105-110
Abstract
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... (More)
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. (Less)
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keywords
KEAP1, Nrf2, NFE2L2, Alzheimer's disease, Cataract, Oxidative stress
in
Mechanisms of Ageing and Development
volume
131
issue
2
pages
105 - 110
publisher
Elsevier
external identifiers
  • wos:000275991600005
  • scopus:77249083614
ISSN
0047-6374
DOI
10.1016/j.mad.2009.12.007
language
English
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yes
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64f1e5ea-ae23-41f8-a23b-55ca28bd6608 (old id 1587321)
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2010-04-22 15:19:19
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2018-05-29 11:02:43
@article{64f1e5ea-ae23-41f8-a23b-55ca28bd6608,
  abstract     = {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.},
  author       = {von Otter, Malin and Landgren, Sara and Nilsson, Staffan and Zetterberg, Madeleine and Celojevic, Dragana and Bergstrom, Petra and Minthon, Lennart and Bogdanovic, Nenad and Andreasen, Niels and Gustafson, Deborah R. and Skoog, Ingmar and Wallin, Anders and Tasa, Gunnar and Blennow, Kaj and Nilsson, Michael and Hammarsten, Ola and Zetterberg, Henrik},
  issn         = {0047-6374},
  keyword      = {KEAP1,Nrf2,NFE2L2,Alzheimer's disease,Cataract,Oxidative stress},
  language     = {eng},
  number       = {2},
  pages        = {105--110},
  publisher    = {Elsevier},
  series       = {Mechanisms of Ageing and Development},
  title        = {Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract},
  url          = {http://dx.doi.org/10.1016/j.mad.2009.12.007},
  volume       = {131},
  year         = {2010},
}