Journal article
Analysis of genetic polymorphisms in the transforming growth factor-β1 gene and the risk of Alzheimer's disease
Human genetics, Vol.106(5), pp.565-569
05/2000
DOI: 10.1007/s004390000313
Abstract
Alzheimer's disease (AD) is a complex disease involving several genetic and environmental components. Genetic studies have yet to identify all the genes involved in the pathogenesis of AD. Transforming growth factor-β1 (TGF-β1) is a candidate gene for AD. It is a multifunctional cytokine whose overexpression has been shown to promote the deposition of amyloid-β peptide. The goal of this study was to investigate the association of three polymorphisms in TGF-β1 with the risk of AD. Two of the polymorphisms are located in the 5' region at positions -800 (G→A) and -509 (C→T), and the third is in exon 5 at codon 263 (Thr→Ile). We screened DNA samples from 428 sporadic, late-onset patients and 421 controls by PCR-based assays. There was no statistically significant difference in genotype or allele frequency distributions between cases and controls for the -800 or codon 263 polymorphisms (P = 0.38 and P = 0.60, respectively). The overall genotype distribution at the -509 site was significantly different between cases and controls. (P = 0.017). The frequency of the -509/TT genotype was significantly higher in AD patients than controls (P = 0.015). We further tested whether this polymorphism may alter the regulation of the TGF-β1 gene using dual luciferase reporter assay. We subcloned the 5' flanking region, which contained the -509 C/T polymorphic sites, in front of the firefly luciferase reporter gene in pGL-3 basic vector and co-transfected with the pRL-CMV vector containing Renilla luciferase gene as a control for transfection efficiency in COS-1 cells. The activity of each promoter allele was directly measured by the ratio of firefly luciferase activity to Renilla luciferase activity. The -509 T allele was associated with marginally higher transcriptional activity of TGF-β compared with the -509 C allele (P = 0.051). These data suggest that the -509 polymorphism of TGF-β1 may be modestly associated with the risk of AD. However, these data should be interpreted with caution as the differences associated with the -509 alleles in both the genetic association and the transfection studies were modest.
Details
- Title: Subtitle
- Analysis of genetic polymorphisms in the transforming growth factor-β1 gene and the risk of Alzheimer's disease
- Creators
- Erin K. Luedecking - University of PittsburghSteven T. DeKosky - University of PittsburghHaider MehdiMary Ganguli - University of PittsburghM. Ilyas Kamboh
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.106(5), pp.565-569
- DOI
- 10.1007/s004390000313
- ISSN
- 0340-6717
- eISSN
- 1432-1203
- Language
- English
- Date published
- 05/2000
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359932902771
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