Journal Article
Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population
Maria Giulia Bacalini; Flavia Palombo; Paolo Garagnani; Cristina Giuliani; Claudio Fiorini; Leonardo Caporali; Michelangelo Stanzani Maserati; Sabina Capellari; Martina Romagnoli; Sara De Fanti; Luisa Benussi; Giuliano Binetti; Roberta Ghidoni; Daniela Galimberti; Elio Scarpini; Marina Arcaro; Enrica Bonanni; Gabriele Siciliano; Michelangelo Maestri; Biancamaria Guarnieri; Federico Cucchiara; Alessandro Schirru; Annalisa Lo Gerfo; Gemma Lombardi; Dario Arnaldi; Pietro Mattioli; Flavio Nobili; Gianluigi Cerroni; Antonella Bartoli; Raffaele Manni; Elena Sinforiani; Michele Terzaghi; Maria Grazia Arena; Rosalia Silvestri; Maria Caterina Di Perri; Ferdinando Franzoni; Gloria Tognoni; Michelangelo Mancuso; Sandro Sorbi; Ubaldo Bonuccelli; Ugo Faraguna; Morena Martucci; Daniela Monti; Valerio Carelli; Claudio Franceschi; Chiara La Morgia; Aurelia Santoro
GeroScience · Vol. 44, Issue 2 · pp. 881-896 · 2022
Abstract
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.