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

Yi Ju Li; Sofia A. Oliveira; Puting Xu; Eden R. Martin; Judith E. Stenger; Clemens R. Scherzer; Michael A. Hauser; William K. Scott; Gary W. Small; Martha A. Nance; Ray L. Watts; Jean P. Hubble; William C. Koller; Rajesh Pahwa; Mathew B. Stern; Bradley C. Hiner; Joseph Jankovic; Christopher G. Goetz; Frank Mastaglia; Lefkos T. Middleton; Allen D. Roses; Ann M. Saunders; Donald E. Schmechel; Steven R. Gullans; Jonathan L. Haines; John R. Gilbert; Jeffrey M. Vance; Margaret A. Pericak-Vance

doi:10.1093/hmg/ddg357

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

Yi Ju Li, Sofia A. Oliveira, Puting Xu, Eden R. Martin, Judith E. Stenger, Clemens R. Scherzer, Michael A. Hauser, William K. Scott, Gary W. Small, Martha A. Nance, Ray L. Watts, Jean P. Hubble, William C. Koller, Rajesh Pahwa, Mathew B. Stern, Bradley C. Hiner, Joseph Jankovic, Christopher G. Goetz, Frank Mastaglia, Lefkos T. MiddletonAllen D. Roses, Ann M. Saunders, Donald E. Schmechel, Steven R. Gullans, Jonathan L. Haines, John R. Gilbert, Jeffrey M. Vance, Margaret A. Pericak-Vance

Hussman Institute for Human Genomics

Research output: Contribution to journal › Article

197 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3259-3267
Number of pages	9
Journal	Human molecular genetics
Volume	12
Issue number	24
DOIs	https://doi.org/10.1093/hmg/ddg357
State	Published - Dec 15 2003

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Li, Y. J., Oliveira, S. A., Xu, P., Martin, E. R., Stenger, J. E., Scherzer, C. R., Hauser, M. A., Scott, W. K., Small, G. W., Nance, M. A., Watts, R. L., Hubble, J. P., Koller, W. C., Pahwa, R., Stern, M. B., Hiner, B. C., Jankovic, J., Goetz, C. G., Mastaglia, F., ... Pericak-Vance, M. A. (2003). Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. Human molecular genetics, 12(24), 3259-3267. https://doi.org/10.1093/hmg/ddg357

Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. / Li, Yi Ju; Oliveira, Sofia A.; Xu, Puting; Martin, Eden R.; Stenger, Judith E.; Scherzer, Clemens R.; Hauser, Michael A.; Scott, William K.; Small, Gary W.; Nance, Martha A.; Watts, Ray L.; Hubble, Jean P.; Koller, William C.; Pahwa, Rajesh; Stern, Mathew B.; Hiner, Bradley C.; Jankovic, Joseph; Goetz, Christopher G.; Mastaglia, Frank; Middleton, Lefkos T.; Roses, Allen D.; Saunders, Ann M.; Schmechel, Donald E.; Gullans, Steven R.; Haines, Jonathan L.; Gilbert, John R.; Vance, Jeffrey M.; Pericak-Vance, Margaret A.

In: Human molecular genetics, Vol. 12, No. 24, 15.12.2003, p. 3259-3267.

Research output: Contribution to journal › Article

Li, YJ, 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 2003, 'Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease', Human molecular genetics, vol. 12, no. 24, pp. 3259-3267. https://doi.org/10.1093/hmg/ddg357

Li, Yi Ju ; Oliveira, Sofia A. ; Xu, Puting ; Martin, Eden R. ; Stenger, Judith E. ; Scherzer, Clemens R. ; Hauser, Michael A. ; Scott, William K. ; Small, Gary W. ; Nance, Martha A. ; Watts, Ray L. ; Hubble, Jean P. ; Koller, William C. ; Pahwa, Rajesh ; Stern, Mathew B. ; Hiner, Bradley C. ; Jankovic, Joseph ; Goetz, Christopher G. ; Mastaglia, Frank ; Middleton, Lefkos T. ; Roses, Allen D. ; Saunders, Ann M. ; Schmechel, Donald E. ; Gullans, Steven R. ; Haines, Jonathan L. ; Gilbert, John R. ; Vance, Jeffrey M. ; Pericak-Vance, Margaret A. / Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease. In: Human molecular genetics. 2003 ; Vol. 12, No. 24. pp. 3259-3267.

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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.",

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T1 - Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease

AU - Li, Yi Ju

AU - Oliveira, Sofia A.

AU - Xu, Puting

AU - Martin, Eden R.

AU - Stenger, Judith E.

AU - Scherzer, Clemens R.

AU - Hauser, Michael A.

AU - Scott, William K.

AU - Small, Gary W.

AU - Nance, Martha A.

AU - Watts, Ray L.

AU - Hubble, Jean P.

AU - Koller, William C.

AU - Pahwa, Rajesh

AU - Stern, Mathew B.

AU - Hiner, Bradley C.

AU - Jankovic, Joseph

AU - Goetz, Christopher G.

AU - Mastaglia, Frank

AU - Middleton, Lefkos T.

AU - Roses, Allen D.

AU - Saunders, Ann M.

AU - Schmechel, Donald E.

AU - Gullans, Steven R.

AU - Haines, Jonathan L.

AU - Gilbert, John R.

AU - Vance, Jeffrey M.

AU - Pericak-Vance, Margaret A.

PY - 2003/12/15

Y1 - 2003/12/15

N2 - 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.

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