Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population

M.G. Bacalini, F. Palombo, P. Garagnani, C. Giuliani, C. Fiorini, L. Caporali, M. Stanzani Maserati, S. Capellari, M. Romagnoli, S. De Fanti, L. Benussi, G. Binetti, R. Ghidoni, D. Galimberti, E. Scarpini, M. Arcaro, E. Bonanni, G. Siciliano, M. Maestri, B. GuarnieriF. Cucchiara, A. Schirru, A. Lo Gerfo, G. Lombardi, D. Arnaldi, P. Mattioli, F. Nobili, G. Cerroni, A. Bartoli, R. Manni, E. Sinforiani, M. Terzaghi, M.G. Arena, R. Silvestri, M.C. Di Perri, F. Franzoni, G. Tognoni, M. Mancuso, S. Sorbi, U. Bonuccelli, U. Faraguna, M. Martucci, D. Monti, V. Carelli, C. Franceschi, C. La Morgia, A. Santoro

Research output: Contribution to journalArticlepeer-review


Many physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.

Original languageEnglish
Pages (from-to)881-896
Number of pages16
Issue number2
Publication statusPublished - 2022


  • aged
  • aging
  • allele
  • Alzheimer disease
  • Article
  • case control study
  • circadian rhythm
  • cohort analysis
  • controlled study
  • exon
  • female
  • gene
  • gene frequency
  • gene identification
  • genetic association
  • genetic polymorphism
  • genetic predisposition
  • genetic susceptibility
  • genetic variability
  • genotype
  • human
  • Italian (citizen)
  • logistic regression analysis
  • longevity
  • major clinical study
  • male
  • matrix assisted laser desorption ionization time of flight mass spectrometry
  • molecular pathology
  • patient selection
  • PER1 gene
  • phenotype
  • population research
  • sequence analysis
  • single nucleotide polymorphism
  • validation process
  • very elderly
  • Aging
  • Alzheimer’s disease
  • Centenarians
  • Circadian rhythms
  • CLOCK genes
  • Polymorphism


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