Lack of Association between Genetic Polymorphism of Circadian Genes (PER2, PER3, CLOCK and OX2R) with Late Onset Depression and Alzheimer's Disease in a Sample of a Brazilian Population (Circadian Genes, Late-Onset Depression and Alzheimer's Disease)

Author(s): Patricia Araújo Pereira, António Alvim-Soares, Maria Aparecida Camargos Bicalho, Edgar Nunes de Moraes, Leandro Malloy-Diniz, Jonas Jardim de Paula, Marco Aurélio Romano-Silva, Debora Marques Miranda

Journal Name: Current Alzheimer Research

Volume 13 , Issue 12 , 2016

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Objectives: This study aims to evaluate the association between polymorphisms in circadian genes and Alzheimer’s disease (AD) and/or late-onset depression (LOD). AD pathology leads to circadian disturbances, with clear negative influence on quality of life. In addition, there is an increasing evidence that regulators of circadian system have effects on AD and LOD pathology.

Design and Subjects: An exploratory case-control study designed to evaluate SNPs in the PER2, PER3, CLOCK and OX2R genes in a sample composed by 249 AD, 222 LOD and 112 healthy individuals.

Measures: The participants were evaluated using DSM-IV criteria for LOD and NINCDS-ADRDA for AD.

Results: In allelic analysis, the OX2R SNP, rs2134294, showed an association of allele C with LOD (p =0.02, OR= 1.6) and AD (p=0.04, OR =1.5). The rs2134294 also showed a genotypic association C/C (p =0.01) for higher risk to develop LOD compared to the control group, with an odd’s ratio of 2.7. The rs9370399 (OX2R) has also shown an association between A allele (p=0.03, OR= 1.4) and AD. These results do not persist after a 1,000 permutations test. For other markers of the OX2R gene and for all other markers of this study no association was found.

Conclusion: In conclusion, the present study found that the investigated Circadian Genes (PER2, PER3, CLOCK and OX2R) polymorphisms were not associated with LOD or AD.

Keywords: Alzheimer's disease (AD), CLOCK, gene, Late-onset depression (LOD), Orexin receptor 2 (OX2R), period homolog (PER), Single-nucleotide polymorphism (SNP).

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Article Details

Year: 2016
Published on: 31 October, 2016
Page: [1397 - 1406]
Pages: 10
DOI: 10.2174/1567205013666160603005630
Price: $65

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