The correlation between genetic factors and freezing of gait in patients with Parkinson's disease.

Autor: Radojević B; Special Hospital for Cerebrovascular Disorders Saint Sava, Belgrade, Serbia. Electronic address: branka022@yahoo.co.uk., Dragašević-Mišković NT; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Marjanović A; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Branković M; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Milovanović A; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Petrović I; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Svetel M; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia., Jančić I; Faculty of Pharmacy, University of Belgrade, Serbia., Stanisavljević D; Institute Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Serbia., Milićević O; Institute Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Serbia., Savić MM; Faculty of Pharmacy, University of Belgrade, Serbia., Kostić VS; Clinic of Neurology, Faculty of Medicine, University of Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Parkinsonism & related disorders [Parkinsonism Relat Disord] 2022 May; Vol. 98, pp. 7-12. Date of Electronic Publication: 2022 Apr 05.
DOI: 10.1016/j.parkreldis.2022.03.018
Abstrakt: Background: Clinical-related risk factors to freezing of gait (FOG) in Parkinson's disease (PD) have been identified. Still, the influence of genetic variations on the FOG occurrence has been poorly studied thus far.
Aim: We aimed to evaluate the association of six selected polymorphisms of DRD2, ANKK1, and COMT genes with the FOG occurrence and explore the influence of ANNK1/DRD2 haplotypes on the onset of FOG in the group of PD patients.
Method: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. FOG was evaluated by posing a direct question. In addition, a comprehensive set of clinical scales was applied to all patients.
Results: FOG occurred in 132 (56.4%) PD patients in our cohort. Freezers were younger at PD onset, had longer disease duration, used higher levodopa daily doses and dopaminergic agents, and had higher motor and non-motor scales scores than non-freezers. FOG was more frequent among AA rs4680 COMT carriers than AG and GG rs4680 COMT carriers. Independent predictors of FOG were: disease duration of more than ten years, levodopa daily dose higher than 500 mg/day, motor status, and COMT AA genotype. AGGAA and GGAAA haplotypes were revealed as protective and vulnerability factors for FOG occurrence.
Conclusion: In addition to previously identified disease- and therapy-related risk factors, our results suggested a possible contribution of dopamine-related genes to the FOG occurrence.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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