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Further evidence for LBP-1c/CP2/LSF association in Alzheimer’s disease families
  1. L Bertram1,
  2. M Parkinson1,
  3. M B McQueen2,
  4. K Mullin1,
  5. M Hsiao1,
  6. R Menon1,
  7. T J Moscarillo3,
  8. D Blacker3,
  9. R E Tanzi1
  1. 1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
  2. 2Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
  3. 3Gerontology Research Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
  1. Correspondence to:
 Dr Rudolph E Tanzi
 Genetics and Aging Research Unit, MGH-East (MIND), 114 16th St., Charlestown, MA 02129, USA; tanzihelix.mgh.harvard.edu

Abstract

Objectives: 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.

  • AD, Alzheimer’s disease
  • CAG, Consortium on Alzheimer’s Genetics
  • CLR, conditional logistic regression
  • LD, linkage disequilibrium
  • OR, odds ratio
  • PDT, pedigree disequilibrium test
  • SNP, single nucleotide polymorphism
  • 95% CI, 95% confidence interval
  • CP2
  • family based association
  • FBAT
  • LBP-1c
  • LSF
  • TFCP2
  • transcription factor CP2

https://doi.org/10.1136/jmg.2004.024596

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    Footnotes

    • This work was sponsored by grants from the NIMH, the NIA (ADRC), and the Alzheimer Association. LB was a fellow of the Deutsche Forschungsgemeinschaft (DFG) and now receives a fellowship from the Harvard Center for Neurodegeneration and Repair (HCNR), Core A, and a stipend from the National Alliance for Research on Schizophrenia and Depression (NARSAD). MBM is supported by a National Research Service Award, Training Program in Psychiatric Epidemiology and Biostatistics (T32 MH17119).

    • Competing interests: none declared