Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
Artikel i vetenskaplig tidskrift, 2014

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.

NFE2L2

risk factor

haplotype

KEAP1

SNP

Nrf2

ALS

Amyotrophic lateral sclerosis

Författare

Petra Bergström

Göteborgs universitet

Malin von Otter

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Ann-Charloth Nilsson

Umeå universitet

Michael Nilsson

Göteborgs universitet

Peter M Andersen

Umeå universitet

Ola Hammarsten

Göteborgs universitet

Henrik Zetterberg

Göteborgs universitet

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

2167-8421 (ISSN) 2167-9223 (eISSN)

Vol. 15 1-2 130-137

Ämneskategorier

Neurovetenskaper

DOI

10.3109/21678421.2013.839708

PubMed

24102512

Mer information

Senast uppdaterat

2018-02-27