Intronic rs2147363 variant in ATP7B transcription factor-binding site associated with Alzheimer's disease

Serena Bucossi, Renato Polimanti, Mariacarla Ventriglia, Stefania Mariani, Mariacristina Siotto, Francesca Ursini, Laura Trotta, Federica Scrascia, Antonio Callea, Fabrizio Vernieri, Rosanna Squitti

Research output: Contribution to journalArticlepeer-review


Copper homeostasis abnormalities have been shown to be associated with Alzheimer's disease (AD), possibly by accelerating amyloid-β toxicity and plaque formation. The ATP7B gene plays a key role in controlling body copper balance. Our previous studies showed an association between ATP7B variants and AD risk. Among these variants, an intronic single nucleotide polymorphism, rs2147363, was associated with AD risk. In order to understand this intronic association, we screened a population of 286 AD patients and 283 healthy controls, and verified the presence of other functional coding variants in linkage disequilibrium (LD). Then we searched for a regulatory function region close to rs2147363. An LD analysis revealed the presence of an LD between rs2147363 and a Wilson's disease-causing variant, rs7334118. However, this mutation did not explain the observed genetic association. Conversely, in silico analyses of rs2147363 functionality highlighted that this variant is located in a binding site of a transcription factor, and is, consequently, associated with regulatory function. These data suggest that the genetic variation in cis-regulatory elements located in non-coding regions can have a role in determining ATP7B functionality and account for some of the AD missing hereditability.

Original languageEnglish
Pages (from-to)453-459
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - 2013


  • Alzheimer's disease
  • ATP7B
  • cis-regulatory element
  • copper
  • intronic variant

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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