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.


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 2 105-110

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