Uncoupling protein 4 (UCP4) gene variability in neurodegenerative disorders: further evidence of association in Frontotemporal dementia.

Uncoupling protein 4 (UCP4) gene variability in neurodegenerative disorders: further evidence of association in Frontotemporal dementia. Aging (Albany NY). 2018 Nov 13;: Authors: Montesanto A, Crocco P, Dato S, Geracitano S, Frangipane F, Colao R, Maletta R, Passarino G, Bruni AC, Rose G Abstract Ongoing research suggests that mitochondrial dysfunction is a common hallmark in neurodegenerative diseases, pointing to mitochondrial uncoupling process as a critical player. We recently reported that rs9472817-C/G, an intronic variant of neuronal mitochondrial uncoupling protein-4 (UCP4/SLC25A27) gene affects the risk of late onset Alzheimer's disease (LOAD), and that the variant's effect is strongly dependent on APOE-ε4 status. Here, we extended our analysis to a cohort of 751 subjects including late-onset familial and sporadic cases of frontotemporal dementia (FTD; 213), Parkinson disease (PD;96), and 442 healthy controls. In all subgroups, carriers of APOE-ε4 allele were at higher risk of disease. Regarding the rs9472817, no association was detected in familial FTD and both subgroups of PD patients. In sporadic FTD, as in LOAD, we found that the C allele increased the risk of disease of about 1.51-fold in a dose-dependent manner (p=0.013) independently from that conferred by APOE-ε4. Expression quantitative trait loci (eQTL) data of different brain regions suggest that rs9472817 likely exerts its effect by a cis-regulatory mechanism ...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research