Association of Nrf2-encoding <it>NFE2L2 </it>haplotypes with Parkinson's disease
<p>Abstract</p> <p>Background</p> <p>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 dis...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Book |
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BMC,
2010-03-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>NFE2L2 </it>and <it>KEAP1</it>, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson's disease.</p> <p>Methods</p> <p>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 <it>NFE2L2 </it>and three representing the variation in <it>KEAP1 </it>were chosen using HapMap data and were genotyped using TaqMan Allelic Discrimination.</p> <p>Results</p> <p>We identified a protective <it>NFE2L2 </it>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 × 10<sup>-6</sup>), 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 <it>KEAP1 </it>did not show any associations.</p> <p>Conclusion</p> <p>These data suggest that variation in <it>NFE2L2 </it>modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.</p> |
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| Item Description: | 10.1186/1471-2350-11-36 1471-2350 |