Further evidence for LBP-1c/CP2/LSF association in Alzheimer's disease families.
OBJECTIVE
Several studies suggested chromosome 12 harbours an Alzheimer's disease (AD) risk factor gene. Significant association of a single nucleotide polymorphism (SNP) in the 3' UTR of transcription factor CP2 (LBP-1c/CP2/LSF or TFCP2) at 12q13 was reported in three independent case-control studies, but no family based analyses have been performed to date.


METHODS
Genotypes for three SNPs were generated in two independent AD family samples. A meta-analysis on all published case-control studies was also performed.


RESULTS
The A allele of the 3' UTR SNP was associated with increased risk for AD in one sample (odds ratio (OR) 2.1, 95% confidence interval (95% CI) 1.1 to 4.3), but not in the other, possibly due to low power. Haplotype analyses showed that this allele is part of a putative risk-haplotype overtransmitted to affected individuals in one sample and in both samples combined. Meta-analysis of the previously associated 3' UTR SNP showed a trend towards a protective effect of the A allele in AD (OR 0.73, 95% CI 0.5 to 1.1).


CONCLUSIONS
This is the first study to examine LBP-1c/CP2/LSF in AD families, and the fifth to independently show significant association. While our results support a role of this gene in AD pathogenesis, the direction of the effect remains uncertain, possibly indicating linkage disequilibrium with another variant nearby.
Bertram
L
L
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Parkinson
M
M
McQueen
M B
MB
Mullin
K
K
Hsiao
M
M
Menon
R
R
Moscarillo
T J
TJ
Blacker
D
D
Tanzi
R E
RE
D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C501906:TFCP2 protein, human; D014157:Transcription Factors