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Association between presenilin-1 -48C/T polymorphism and Down's syndrome
Paola Lucarelli1, Antonella Piciullo, Mariella Palmarino
1Institute of Molecular Biology and Pathology, National Research Council, Rome 00185, Italy.
Neuroscience Letters
|August 17, 2004
Summary
Individuals with Down's syndrome (DS) over 40 may develop Alzheimer's disease (AD) changes. A specific PSEN1 gene polymorphism (-48C/T) showed a lower frequency in DS patients, suggesting a potential genetic link to dementia risk.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Individuals with Down's syndrome (DS), characterized by trisomy 21, exhibit a high likelihood of developing Alzheimer's disease (AD) neuropathology after age 40.
- Shared genetic factors on chromosome 21 are implicated in both DS and AD, yet specific genetic determinants remain undefined.
- The -48C/T polymorphism in the PSEN1 gene promoter is a candidate due to its association with early-onset AD risk.
Purpose of the Study:
- To investigate the association between the -48C/T polymorphism in the PSEN1 gene promoter and Down's syndrome.
- To determine if altered distribution of this polymorphism contributes to the increased dementia prevalence in DS.
Main Methods:
- Recruitment of 260 DS patients and 197 controls with comparable age and gender distributions.
- Extraction of high-molecular-weight DNA from whole blood samples.
- Genotyping of the -48C/T polymorphism in the PSEN1 promoter and comparison of allele and genotype frequencies between DS cases and controls.
Main Results:
- DS cases were less likely to possess the CC genotype compared to controls (P = 0.05).
- A significant difference in allele distribution was observed, with DS patients showing a lower frequency of the C allele (OR: 0.57; P = 0.01).
- No significant interactions were found between PSEN1 polymorphism and age, gender, ApoE, or -850 TNF-alpha polymorphisms.
Conclusions:
- The -48C/T polymorphism in the PSEN1 gene promoter is associated with Down's syndrome.
- This polymorphism, known to modulate amyloid beta load in AD, may influence dementia risk in DS.
- Further research is needed to clarify the precise biological role of this polymorphism in DS-related dementia.