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Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.

Petra Bergström ; Malin von Otter ; Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Ann-Charloth Nilsson ; Michael Nilsson ; Peter M Andersen ; Ola Hammarsten ; Henrik Zetterberg
Amyotrophic lateral sclerosis & frontotemporal degeneration (2167-9223). Vol. 15 (2014), 1-2, p. 130-137.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: Amyotrophic lateral sclerosis, ALS, Nrf2, NFE2L2, KEAP1, SNP, haplotype, risk factor



Denna post skapades 2013-12-05. Senast ändrad 2016-06-29.
CPL Pubid: 188379

 

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Institutioner (Chalmers)

Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin (GU)
Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)
Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering (GU)

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Neurokemi

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