Distribución de polimorfismos de genes de autofagia en una población de enfermos de Parkinson

Zusammenfassung

Parkinson's disease is a progressive neurodegenerative disease, sometimes sporadic. In sporadic PD, genetic and environmental factors interact. Autophagy is a cellular degradative process, mediated by related proteins named ATG. The genes ATG16L1, ATG5, ATG7, ATG10, and ATG12 are essential in phagophore elongation, and the LAMP-2 gene is required in autophagosome-lysosome fusion, essential for the autophagic process, for which it is necessary to analyse genetic variants of these promoters. The promoters of ATG161L, ATG5 and LAMP-2, in patients with sporadic PD, have been related to the gene expression of ATG proteins. These studies have not so far been referred to the Spanish population, which justifies this thesis. The aim was to study the genetic variation of the mentioned promoters. Molecular technical methods were used to detect polymorphisms and variants were associated with sporadic PD. Sequencing methods shown an increased genetic variability in ATG16L1 haplotypes, some being exclusive to patients. In silico analyses were useful to relate polymorphisms with binding to transcription factors. The ATG16L1, ATG5 and LAMP-2 promoters compared with previous studies had 50%, 29% and 60%, respectively, of polymorphic sites. Exceptionally, was obtained significant differences only for the Loc4 of ATG16L1, suggesting a discrepancy between the studied groups. Finally, the importance of detecting genetic diversity in promoters related to autophagy and the role of ethnic group are shown.