@article{fd78b0ef96ae4434a18cc06a5870804d,
title = "Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease",
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 RD 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 = 0007) 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-1β. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.",
author = "Li, {Yi Ju} and Oliveira, {Sofia A.} and Puting Xu and Martin, {Eden R.} and Stenger, {Judith E.} and Scherzer, {Clemens R.} and Hauser, {Michael A.} and Scott, {William K.} and Small, {Gary W.} and Nance, {Martha A.} and Watts, {Ray L.} and Hubble, {Jean P.} and Koller, {William C.} and Rajesh Pahwa and Stern, {Mathew B.} and Hiner, {Bradley C.} and Joseph Jankovic and Goetz, {Christopher G.} and Frank Mastaglia and Middleton, {Lefkos T.} and Roses, {Allen D.} and Saunders, {Ann M.} and Schmechel, {Donald E.} and Gullans, {Steven R.} and Haines, {Jonathan L.} and Gilbert, {John R.} and Vance, {Jeffrey M.} and Pericak-Vance, {Margaret A.}",
note = "Funding Information: We thank the patients with Alzheimer and Parkinson disease and their families whose help and participation made this work possible. We also thank Dr Fred H. Allen of the Carolina Neurology Clinic, as well as the clinical and research personnel of the Center for Human Genetics at Duke University Medical Center, the Program in Human Genetics at Vanderbilt University Medical Center, and the Joseph and the Kathleen Bryan ADRC. We would especially like to thank Ms Katherine Lewis for her skillful editing. This work was supported by an American Federation for Aging Research (AFAR) 2002 Research Grant; a New Investigator Research Grant Award (Hilles Families Foundation Award), grants IIRG94101, IRG2-96044 and IIRG-00-2006, a T.L.L. Temple Award (TLL-97-012) and a Zenith Award (ZEN-01-2935) from the Alzheimer{\textquoteright}s Association; the 2001 Louis D award from the Institut de France; grants NS31153, AG05128, AG13308, AG11268, AG10123, AG19085, MH52453, MH59528, NS031153, NS26630 and NS39764 from the National Institutes of Health; grant RR00865 from the US Public Health Service; grant 95-23330 from the California Department of Health Services; the Fran and Ray Stark Foundation Fund for Alzheimer{\textquoteright}s Disease Research; and GlaxoSmithKline Inc. S.A.O. received support from a post-doctoral fellowship (BPD/5733/2001), granted by the Portuguese Science and Technology Foundation.",
year = "2003",
month = dec,
day = "15",
doi = "10.1093/hmg/ddg357",
language = "English (US)",
volume = "12",
pages = "3259--3267",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "24",
}