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Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer’s disease and longevity in an Italian population
GeroScience ( IF 5.6 ) Pub Date : 2021-12-18 , DOI: 10.1007/s11357-021-00477-0
Maria Giulia Bacalini 1 , Flavia Palombo 2 , Paolo Garagnani 3, 4, 5, 6, 7 , Cristina Giuliani 7, 8 , Claudio Fiorini 2 , Leonardo Caporali 2 , Michelangelo Stanzani Maserati 9 , Sabina Capellari 9, 10 , Martina Romagnoli 2 , Sara De Fanti 7, 8 , Luisa Benussi 11 , Giuliano Binetti 11 , Roberta Ghidoni 11 , Daniela Galimberti 12, 13 , Elio Scarpini 12, 13 , Marina Arcaro 12 , Enrica Bonanni 14 , Gabriele Siciliano 14 , Michelangelo Maestri 14 , Biancamaria Guarnieri 15 , , Morena Martucci 3 , Daniela Monti 16 , Valerio Carelli 2, 10 , Claudio Franceschi 3, 17 , Chiara La Morgia 2, 9 , Aurelia Santoro 3, 7
Affiliation  

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.



中文翻译:

生物钟基因 PER1 中 rs3027178 多态性与意大利人群阿尔茨海默病易感性和长寿的关联

人体中的许多生理过程都遵循由生物钟系统控制的 24 小时昼夜节律。由视网膜感知的光是主要的“时代”,能够使昼夜节律与明暗周期同步。昼夜节律功能障碍和睡眠障碍与衰老和神经退行性疾病有关,包括轻度认知障碍 (MCI) 和阿尔茨海默病 (AD)。在本研究中,我们旨在研究与来自意大利的健康对照相比,AD 患者时钟基因的遗传变异性。我们还包括了一组意大利百岁老人,考虑到他们成功衰老的极端表型,他们在关联研究中被视为超级对照。我们分析了与昼夜节律相关的八十四个基因的外显子序列,并且通过基质辅助激光解吸/电离-飞行时间质谱法在更大的独立AD患者队列中进一步评估了在第一个发现阶段确定的最重要的变体。结果确定了 rs3027178 多态性在PER1昼夜节律基因与 AD,G 等位基因对 AD 具有保护作用。有趣的是,rs3027178 在 AD 患者和百岁老人中显示出相似的基因型频率。这些结果共同强调了昼夜节律功能障碍与 AD 易感性的相关性,并有助于讨论年龄相关疾病的遗传学与长寿之间的关系的作用。

更新日期:2021-12-18
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