Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract.
Journal article, 2010
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 (p(c)=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.
Author
Malin von Otter
University of Gothenburg
Sara Landgren
University of Gothenburg
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
Madeleine Zetterberg
University of Gothenburg
Dragana Celojevic
University of Gothenburg
Petra Bergström
University of Gothenburg
L. Minthon
Lund University
Nenad Bogdanovic
Karolinska Institutet
Niels Andreasen
Karolinska Institutet
Deborah Gustafson
University of Gothenburg
Ingmar Skoog
University of Gothenburg
Anders Wallin
University of Gothenburg
Gunnar Tasa
University of Tartu
Kaj Blennow
University of Gothenburg
Michael Nilsson
University of Gothenburg
Ola Hammarsten
University of Gothenburg
Henrik Zetterberg
University of Gothenburg
Mechanisms of ageing and development
1872-6216 (ISSN)
Vol. 131 2 105-110Subject Categories
Physiology
Psychiatry
Other Basic Medicine
DOI
10.1016/j.mad.2009.12.007
PubMed
20064547