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Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease.

Malin von Otter ; Sara Landgren ; Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Dragana Celojevic ; Petra Bergström ; Anna Håkansson ; Hans Nissbrandt ; Marek Drozdzik ; Monika Bialecka ; Mateusz Kurzawski ; Kaj Blennow ; Michael Nilsson ; Ola Hammarsten ; Henrik Zetterberg
BMC medical genetics (1471-2350). Vol. 11 (2010), p. 36.
[Artikel, refereegranskad vetenskaplig]

BACKGROUND: Oxidative stress is heavily implicated in the pathogenic process of Parkinson's disease. Varying capacity to detoxify radical oxygen species through induction of phase II antioxidant enzymes in substantia nigra may influence disease risk. Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease. METHODS: The study included a Swedish discovery case-control material (165 cases and 190 controls) and a Polish replication case-control material (192 cases and 192 controls). Eight tag single nucleotide polymorphisms representing the variation in NFE2L2 and three representing the variation in KEAP1 were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination. RESULTS: We identified a protective NFE2L2 haplotype in both of our European case-control materials. Each haplotype allele was associated with five years later age at onset of the disease (p = 0.001) in the Swedish material, and decreased risk of PD (p = 2 x 10(-6)), with an odds ratio of 0.4 (95% CI 0.3-0.6) for heterozygous and 0.2 (95% CI 0.1-0.4) for homozygous carriers, in the Polish material. The identified haplotype includes a functional promoter haplotype previously associated with high transcriptional activity. Genetic variation in KEAP1 did not show any associations. CONCLUSION: These data suggest that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.



Denna post skapades 2010-04-19. Senast ändrad 2015-01-16.
CPL Pubid: 120045

 

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Institutioner (Chalmers)

Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (GU)
Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)
Institutionen för biomedicin (GU)
Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering (2006-2016)
Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin (GU)

Ämnesområden

Fysiologi
Psykiatri

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