Abstract
Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1×10 -6, odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10 -11). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD.
| Original language | English |
|---|---|
| Journal | Neurobiology of Aging |
| Volume | 33 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2012 |
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Keywords
- Alzheimer's disease
- Amyloid precursor protein
- Association
- Cdx-2
- Functional polymorphism
- Vitamin D receptor
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Aging
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Vitamin D receptor and Alzheimer's disease : A genetic and functional study. / Wang, Liyong; Hara, Kenju; Van Baaren, Jessica M.; Price, Justin C.; Beecham, Gary W; Gallins, Paul J.; Whitehead, Patrice L.; Wang, Gaofeng; Lu, Chunrong; Slifer, Michael A.; Zuchner, Stephan L; Martin, Eden R; Mash, Deborah C; Haines, Jonathan L.; Pericak-Vance, Margaret A; Gilbert, John.
In: Neurobiology of Aging, Vol. 33, No. 8, 01.08.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vitamin D receptor and Alzheimer's disease
T2 - A genetic and functional study
AU - Wang, Liyong
AU - Hara, Kenju
AU - Van Baaren, Jessica M.
AU - Price, Justin C.
AU - Beecham, Gary W
AU - Gallins, Paul J.
AU - Whitehead, Patrice L.
AU - Wang, Gaofeng
AU - Lu, Chunrong
AU - Slifer, Michael A.
AU - Zuchner, Stephan L
AU - Martin, Eden R
AU - Mash, Deborah C
AU - Haines, Jonathan L.
AU - Pericak-Vance, Margaret A
AU - Gilbert, John
PY - 2012/8/1
Y1 - 2012/8/1
N2 - Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1×10 -6, odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10 -11). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD.
AB - Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1×10 -6, odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10 -11). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Association
KW - Cdx-2
KW - Functional polymorphism
KW - Vitamin D receptor
UR - http://www.scopus.com/inward/record.url?scp=84862805905&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862805905&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2011.12.038
DO - 10.1016/j.neurobiolaging.2011.12.038
M3 - Article
VL - 33
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 8
ER -