Intergenic Interactions of ESR1, GSTO1 and AGER and Risk of Dementia in Community-Dwelling Elderly (SADEM Study)

Dementia causes the loss of functional independence, resulting in a decrease in the quality of life of those who suffer from it.

This study aimed to investigate the interactions influencing susceptibility to the development of dementia through multifactor dimensionality reduction (MDR).

the study population was made up of 221 cases and 534 controls. We performed an MDR analysis as well as a bioinformatic analysis to identify interactions between the genes GSTO1_rs4925, AGER_rs2070600, and ESR1_rs3844508 associated with susceptibility to dementia.

We observed associations between the polymorphism of GSTO1 and risk of dementia for the site rs4925 with the recessive model (OR = 1.720, 95% CI = 1.166-2.537 p = 0.006). Similarly, the site AGER rs2070600 showed risk of dementia with an additive model of inheritance (OR = 7.278, 95% CI = 3.140-16.868; p < 0.001). Furthermore, we identified the best risk model with a high precision of 79.6% that, when combined with three environmental risk factors, did not give an OR = 26.662 95%CI (16.164-43.979) with p < 0.001.

The MDR and bioinformatics results provide new information on the molecular pathogenesis of dementia, allowing identification of possible diagnostic markers and new therapeutic targets.