PIN1 promoter polymorphisms are associated with Alzheimer's disease

Neurobiol Aging. 2007 Jan;28(1):69-74. doi: 10.1016/j.neurobiolaging.2005.11.009. Epub 2005 Dec 27.


In our study, we analyzed the coding and promoter regions of the PIN1 gene in a group of 111 Alzheimer's disease (AD) patients looking for a possible genotype-phenotype correlation. The presence of SNPs - which could affect and modify the clinical phenotype of AD patients was also investigated. We identified two single nucleotide polymorphisms (SNPs) at positions -842 (G-->C) and -667 (C-->T) in the promoter region of the PIN1 gene. Our results evidenced a significantly higher percentage of -842C allele carriers in AD subjects with respect to healthy controls. We found that this allele significantly raised the risk of developing AD (OR 3.044, CI 1.42-6.52). The -842 and -667 SNPs were in linkage disequilibrium and combined to form haplotypes. The CC haplotype conferred a higher risk of developing AD (OR 2.95, confidence interval 1.31-6.82). Finally, protein expression analyses revealed that subjects carrying the -842 CC genotype or the CC haplotype showed reduced levels of the PIN1 protein in peripheral mononuclear cells.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Biomarkers / analysis
  • DNA Mutational Analysis / methods
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing / methods*
  • Genotype
  • Heterozygote
  • Humans
  • Incidence
  • Italy / epidemiology
  • Male
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Risk Assessment / methods*
  • Risk Factors


  • Biomarkers
  • NIMA-Interacting Peptidylprolyl Isomerase
  • PIN1 protein, human
  • Peptidylprolyl Isomerase