Cibulka M1, Brodňanová M1, Grendár M1, Necpal J2, Škorvánek M3, Haň V3, Veselý B4, Benetín J5, Kurča E6, Grofik M6, Kolísek M1
1Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, CU in Bratislava
2Clinic of Neurology, Agel hospital, Zvolen
3Clinic of Neurology, L. Pasteur University hospital, Košice
4Clinic of Neurology, Faculty hospital Nitra, Nitra
5Clinic of Neurology, University hospital Bratislava, Bratislava
6Clinic of Neurology, University hospital Martin, Martin
Introduction: Parkinson's disease (PD) is a highly prevalent neurodegenerative disease of elderly patients. The main risk factors for the development of this treatable but incurable disease are advanced age and male sex. The pathogenesis of the idiopathic form of PD is multifactorial. Genetic predisposition as well as environmental factors play a key role in the development of the disease. Recently, the attention of the scientific world has been focused on the possible association of deviations in Mg2+ homeostasis with the pathogenesis of PD. The SLC41A1 gene, encoding the eponymous sodium-magnesium exchanger, has been identified as one of the genes located within the PARK16 locus. This locus has been associated with the risk of PD development in several populations. The aim of our multicentric study was to analyze the association of the presence of single nucleotide variants of the ORF region (rs11240569, rs708727, and rs823156) of SLC41A1 with the risk of PD development.
Materials and methods: DNA samples of 508 patients diagnosed with PD from the Centers for Extrapyramidal Diseases in Martin, Zvolen, Košice, Nitra and Bratislava were analyzed in the study. DNA samples from 472 individuals who were included in the study based on defined inclusion and exclusion criteria were used as controls. Variants in the ORF region were identified using TaqMan® probes by qPCR. The obtained data were analyzed by frequentist statistics as well as by machine learning approaches in the Random Forest algorithm.
Results: By analyzing the data in the dominant (GG vs. GA+AA) and completely over-dominant (GG+AA vs. GA) models, we found that the rs708727 variant was significantly (p<0.05) associated with an increased risk of developing PD. The remaining variants and haplotypes did not show significant correlation with the risk of PD development. The presence of any of the variants did not influence the age of onset of the disease.
Conclusions: The results of our study support the theory linking Mg2+ homeostasis to the etiopathogenesis of PD. The rs708727 variant and its effect on PM20D1 expression may partly explain the pathogenesis of dementia that often develops in patients with PD.
