Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract.
Artikel i vetenskaplig tidskrift, 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.
Författare
Malin von Otter
Göteborgs universitet
Sara Landgren
Göteborgs universitet
Staffan Nilsson
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Matematisk statistik
Madeleine Zetterberg
Göteborgs universitet
Dragana Celojevic
Göteborgs universitet
Petra Bergström
Göteborgs universitet
L. Minthon
Lunds universitet
Nenad Bogdanovic
Karolinska Institutet
Niels Andreasen
Karolinska Institutet
Deborah Gustafson
Göteborgs universitet
Ingmar Skoog
Göteborgs universitet
Anders Wallin
Göteborgs universitet
Gunnar Tasa
Tartu Ülikool
Kaj Blennow
Göteborgs universitet
Michael Nilsson
Göteborgs universitet
Ola Hammarsten
Göteborgs universitet
Henrik Zetterberg
Göteborgs universitet
Mechanisms of ageing and development
1872-6216 (ISSN)
Vol. 131 2 105-110Ämneskategorier
Fysiologi
Psykiatri
Annan medicinsk grundvetenskap
DOI
10.1016/j.mad.2009.12.007
PubMed
20064547