A TGF-β1 polymorphism association with dementia and neuropathologies: The HAAS

Peila, Rita; Yucesoy, Berran; White, Lon R.; Johnson, Victor; Kashon, Michael L.; Wu, Kim; Petrovitch, Helen; Luster, Michael; Launer, Lenore J.

doi:10.1016/j.neurobiolaging.2006.06.004

« Previous Next »Neurobiology of Aging
Volume 28, Issue 9 , Pages 1367-1373, September 2007

A TGF-β1 polymorphism association with dementia and neuropathologies: The HAAS

Rita Peila
- Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Suite 3C-309, Bethesda, 20892-9205 MD, USA
- Pacific Health Research Institute, 846 South Hotel Street, Suite 307, Honolulu, HI 96813, USA
- Tel.: 1 301 496 1178.
- Tel.: 1 808 564 5420.
- Corresponding author. Tel.: +1 301 496 6292; fax: +1 301 496 4006.
Berran Yucesoy
- Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, USA
- Tel.: 1 304 285 5993.
Lon R. White
- Pacific Health Research Institute, 846 South Hotel Street, Suite 307, Honolulu, HI 96813, USA
- Department of Geriatric Medicine, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
- Tel.: 1 808 564 5420.
- Tel.: 1 808 564 5421.
Victor Johnson
- Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, USA
- Tel.: 1 304 285 5993.
Michael L. Kashon
- Biostatistic Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
- Tel.: 1 304 285 6209.
Kim Wu
- Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Suite 3C-309, Bethesda, 20892-9205 MD, USA
- Tel.: 1 301 496 1178.
Helen Petrovitch
- Pacific Health Research Institute, 846 South Hotel Street, Suite 307, Honolulu, HI 96813, USA
- Tel.: 1 808 564 5420.
Michael Luster
- Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, USA
- Tel.: 1 304 285 5993.
Lenore J. Launer
- Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Avenue, Suite 3C-309, Bethesda, 20892-9205 MD, USA
- Tel.: 1 301 496 1178.

Received 27 February 2006; received in revised form 1 June 2006; accepted 7 June 2006. published online 10 August 2006.

Abstract

The transforming growth factor-β1 (TGF-β1) is involved in post-ischemic neuronal rescue and in β-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-β1 functional genetic variants. The association of the TGF-β1+29T→C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (OR_TC=0.28, 95% confidence interval (CI): 0.1–0.9; OR_CC=0.28, CI: 0.1–0.9), microinfarcts (OR_CC=0.31, CI: 0.13–0.71) and cerebral amyloid angiopathy (OR_CC=0.48, CI: 0.2–0.9). The CC genotype was associated with an increase risk of neocortical plaques (OR_CC=4.34, CI: 1.6–11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia.