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Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.

Publication ,  Journal Article
Li, Y-J; Oliveira, SA; Xu, P; Martin, ER; Stenger, JE; Scherzer, CR; Hauser, MA; Scott, WK; Small, GW; Nance, MA; Watts, RL; Hubble, JP ...
Published in: Hum Mol Genet
December 15, 2003

We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.

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Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

December 15, 2003

Volume

12

Issue

24

Start / End Page

3259 / 3267

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Lod Score
  • Linkage Disequilibrium
  • Humans
  • Glutathione Transferase
  • Genetics & Heredity
 

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Li, Y.-J., Oliveira, S. A., Xu, P., Martin, E. R., Stenger, J. E., Scherzer, C. R., … Welsh-Bohmer, K. A. (2003). Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. Hum Mol Genet, 12(24), 3259–3267. https://doi.org/10.1093/hmg/ddg357
Li, Yi-Ju, Sofia A. Oliveira, Puting Xu, Eden R. Martin, Judith E. Stenger, Clemens R. Scherzer, Michael A. Hauser, et al. “Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.Hum Mol Genet 12, no. 24 (December 15, 2003): 3259–67. https://doi.org/10.1093/hmg/ddg357.
Li Y-J, Oliveira SA, Xu P, Martin ER, Stenger JE, Scherzer CR, et al. Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. Hum Mol Genet. 2003 Dec 15;12(24):3259–67.
Li, Yi-Ju, et al. “Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease.Hum Mol Genet, vol. 12, no. 24, Dec. 2003, pp. 3259–67. Pubmed, doi:10.1093/hmg/ddg357.
Li Y-J, Oliveira SA, Xu P, Martin ER, Stenger JE, Scherzer CR, Hauser MA, Scott WK, Small GW, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Goetz CG, Mastaglia F, Middleton LT, Roses AD, Saunders AM, Schmechel DE, Gullans SR, Haines JL, Gilbert JR, Vance JM, Pericak-Vance MA, Hulette C, Welsh-Bohmer KA. Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. Hum Mol Genet. 2003 Dec 15;12(24):3259–3267.
Journal cover image

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

December 15, 2003

Volume

12

Issue

24

Start / End Page

3259 / 3267

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Parkinson Disease
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Lod Score
  • Linkage Disequilibrium
  • Humans
  • Glutathione Transferase
  • Genetics & Heredity