Change search
ReferencesLink to record
Permanent link

Direct link
Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis
Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Institute of Mathematical Sciences, Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Show others and affiliations
2014 (English)In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, Vol. 15, no 1-2, 130-137 p.Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.

Place, publisher, year, edition, pages
Informa Healthcare, 2014. Vol. 15, no 1-2, 130-137 p.
Keyword [en]
Amyotrophic lateral sclerosis, ALS, Nrf2, NFE2L2, KEAP1, SNP, haplotype, risk factor
National Category
Neurosciences Neurology
URN: urn:nbn:se:umu:diva-87634DOI: 10.3109/21678421.2013.839708ISI: 000332417000018OAI: diva2:711579
Available from: 2014-04-10 Created: 2014-04-07 Last updated: 2014-04-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Nilsson, Ann-CharlothAndersen, Peter
By organisation
Clinical Neuroscience

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 72 hits
ReferencesLink to record
Permanent link

Direct link