Complement receptor 1 coding variant p.Ser1610Thr in Alzheimer's disease and related endophenotypes
Caroline Van Cauwenberghe1, Karolien Bettens, Sebastiaan Engelborghs
1Department of Molecular Genetics, VIB, Antwerp, Belgium.
Neurobiology of Aging
|April 16, 2013
Summary
A rare complement receptor 1 (CR1) variant (p.Ser1610Thr) is not linked to Alzheimer disease (AD) risk or related biomarkers. Our findings support a CR1 copy number variation (CNV) as the primary risk factor for AD in this population.
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- A functional copy number variation (CNV) in complement receptor 1 (CR1) has been previously associated with Alzheimer disease (AD) risk.
- A recent study identified a rare CR1 coding variant (p.Ser1610Thr, rs4844609) potentially explaining the association of a top genome-wide association (GWA) single nucleotide polymorphism (SNP) with AD susceptibility.
Purpose of the Study:
- To investigate the role of the CR1 p.Ser1610Thr variant in AD pathogenesis and its association with AD-related endophenotypes.
- To determine if the p.Ser1610Thr variant, rather than the CR1 CNV, explains the observed CR1 association with AD in a Flanders-Belgian cohort.
Main Methods:
- Genotyping of the CR1 p.Ser1610Thr variant in a Flanders-Belgian cohort.
- Association analysis of the variant with AD diagnosis and endophenotypes (memory impairment, tau, amyloid-beta levels).
- Evaluation of the variant's role in explaining the association signals of GWA SNPs (rs3818361/rs6656401) and the CR1 CNV with AD.
Main Results:
- The CR1 p.Ser1610Thr variant was not associated with AD, memory impairment, total tau, amyloid β(1-42), or phosphorylated tau levels.
- This variant did not account for the association of GWA SNPs (rs3818361/rs6656401) or the CR1 CNV with AD in the cohort.
- The CR1 CNV and the GWA SNPs (rs3818361/rs6656401) represented the same association signal.
Conclusions:
- The CR1 p.Ser1610Thr variant is unlikely to play a significant role in AD risk or related endophenotypes.
- These findings reaffirm the CR1 CNV as a potential functional risk factor for AD, explaining the genetic association of CR1 with the disease.
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