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Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
- Source :
- Human molecular genetics. 12(24)
- Publication Year :
- 2003
-
Abstract
- 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.
- Subjects :
- Male
Candidate gene
medicine.medical_specialty
Single-nucleotide polymorphism
Disease
Biology
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Genetic linkage
Alzheimer Disease
Internal medicine
Molecular genetics
Genetics
medicine
Humans
Age of Onset
Molecular Biology
Genetics (clinical)
Genetic association
Aged
Glutathione Transferase
Oligonucleotide Array Sequence Analysis
Chromosomes, Human, Pair 10
Proteolytic enzymes
Glutathione S-transferase omega 1
Chromosome Mapping
Parkinson Disease
General Medicine
Middle Aged
medicine.disease
Endocrinology
Female
Age of onset
Alzheimer's disease
Lod Score
Candidate Disease Gene
Subjects
Details
- ISSN :
- 09646906
- Volume :
- 12
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Human molecular genetics
- Accession number :
- edsair.doi.dedup.....1ee2a4761453fee9d24a545f7dc8f99f