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.