Effect of TGF-beta 1 genetic variability on small vessel ischemia and vascular dementia: The Honolulu-Asia aging study.
Peila-R; Yucesoy-B; Wu-K; Luster-M; White-L; Launer-LJ
Neurobiol Aging 2004 Jul; 25(Suppl 2):S539
Background: Cerebral ischemia can lead to local hypoxia, neurodegeneration and vascular dementia. Pro- and anti-inflammatory processes contribute the progression of vascular damage. Experimentally, the cytokine transforming growth factor-beta 1 (TGF-beta 1) has shown to protect neurons in ischemic events. The genetic variants that influence the protein level of this cytokine could modify the risk for vascular lesions and dementia. Objective(s): To examine the association of the polymorptfism TGF-beta 1+29 (T --> C) with vascular dementia (VaD) and ischemic lesions identified in antopsied brain tissue. Methods: Data are from the Honolulu-Asia Aging Study (HAAS) a dementia study of Japanese American men. As a part of the HAAS, subjects were invited to enroll in an autopsy progarn. We used a nested case-control sample of 293 dementia cases, including 99 cases of VaD, and 491 controls randomly selected to frequency match the cases for age. Dementia was assessed in 1991 and 1994 by a multistep protocol. VaD was diagnosed according to the California Alzheimer's Disease Diagnostic and Treatment Centers guidelines. Autopsy data on brain micro, small and large infarcts were available on 282 cases and controls. Blood samples for the genotype analysis were collected in 1991. Logistic regression was used to assess the odds ratio (OR) for VaD after adjustment for age, education and several vascular-related risk factors; the analyses for cerebral vascular lesions were adjusted for age at death, education and vascular-related risk factors. Results: Compared to the more common TT genotype the mutant allele C was associated with a reduced risk for VaD (ORtc = 0.28, 95% confidence interval (CI) 0.09-0.91; ORcc = 0.28, CI 0.09-0.89). Compared to the TT genotype, the CC genotype showed reduced levels of micro infarcts (ORtc = 0.87, CI 0.43-1.75 and ORcc = 0.31, CI 0.13-0.71) and small infarcts (ORtc = 0.58, CI 0.31-1.09 and ORcc = 0.62, CI 0.31-1.23). Large infarcts were not associated with any allelic variant of the TGF-beta 1+29 potymorphism. Conclusions: The T allele of the TGF-beta 1+29 polymorphism may reduce the risk for VaD. The anatomical basis for this association may be the reduction of the risk for small vessel ischemic events.
Mathematical-models; Analytical-methods; Statistical-analysis; Vasomotor-system-disorders; Neurological-diseases; Neurological-reactions; Neurovascular-disorders; Neurological-system; Cerebrovascular-system; Cerebrovascular-system-disorders; Age-factors; Age-groups
Abstract; Conference/Symposia Proceedings
Neurobiology of Aging: Abstracts from the 9th International Conference on Alzheimer's Disease and Related Disorders,Philadelphia, Pennsylvania, 17-22 July 2004