Category: Parkinson's Disease: Genetics
Objective: We aimed to evaluate the association of six selected polymorphism of DRD2, ANKK1, and COMT genes with the occurrence of freeying of gate (FOG), and to explore the influence of ANNK1/DRD2 haplotypes on the onset of FOG in group of PD patients.
Background: Demographic and clinical risk factors related to FOG have been identified, but the influence of genetic variations on the occurrence of FOG has been very poorly studied thus far.
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. Each patient underwent comprehensive neurological examination, as well as screening of depression, anxiety and cognitive status.
Results: In our cohort, FOG occurred in 132 (56.4%) PD patients. Freezers were younger at PD onset, had longer disease duration, used higher levodopa daily doses and dopaminergic agents, had higher scores of the motor and non-motor scales compared to non-freezers. FOG was more frequent among AA rs4680 COMT carriers when compared to AG and GG rs4680 COMT carriers. Independent predictors of FOG were: disease duration more than 10 years, levodopa daily dose higher than 500 mg/day, motor status, and COMT AA genotype. AGGAA and GGAAA haplotype served as a protective and a vulnerability factor, respectively, for FOG occurrence.
Conclusion: In addition to previously identified disease- and therapy-related risk factors, our results suggested a possible genetic contribution to the etiology of FOG.
References: [1] Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol 2011; 10:734–44.
[2] Giladi N, McMahon D, Przedborski S, Flaster E, Guillori S, Kostic V, et al. Motor blocks in Parkinson’s disease. Neurology 1992; 42:333–9.
[3] Schaafsma JD, Balash Y, Gurevich T, Bartels AL, Hausdorff JM, Giladi N. Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson’s disease. Eur J Neurol. 2003;10(4):391–8.
[4] Okuma Y, Yanagisawa N, The clinical spectrum of freezing of gait in Parkinson’s disease. Mov Disord. 2008; 23(11):1639-40.
[5] Pozzi NG, Canessa A, Palmisano C, Brumberg J, Steigerwald F, Reich MM, Minafra B, Pacchetti C, Pezzoli G, Volkmann J and Isaias IU. Freezing of gait in Parkinson’s disease reflects a sudden derangement of locomotor network dynamics. Brain. 2019; 142: 2037–2050.
[6] Plotnik M, Hausdorff JM. The role of gait rhythmicity and bilateral coordination of stepping in the pathophysiology of freezing of gait in Parkinson’s disease. Mov Disord. 2008; 23:S444–S450.
[7] Cowie D, Limousin P, Peters A, Day BL. Insights into the neural control of locomotion from walking through doorways in Parkinson’s disease. Neuropsychologia. 2010; 48:2750–2757.
[8] Naismith SL, Shine JM, Lewis SJ. The specific contributions of set-shifting to freezing of gait in Parkinson’s disease. Mov Disord. 2010; 25:1000–1004.
[9] Yogev G, Plotnik M, Peretz C, Giladi N, Hausdorff JM. Gait asymmetry in patients with Parkinson’s disease and elderly fallers: when does the bilateral coordination of gait require attention? Exp Brain Res. 2007; 177:336–346.
[10] Forsaa EB, Larsen JP, Wentzel-Larsen , Alves G. A 12-year population-based study of freezing of gait in Parkinson’s disease. Parkinsonism Relat Disord. 2015; 21(3):254–8.
[11] Zhang H, Yin X, Ouyang Z, Chen J, Zhou S, Zhang C, Pan X, Wang S, Yang J, Feng Y, et al. A prospective study of freezing of gait with early Parkinson disease in Chinese patients. Medicine. 2016;95(26):e4056.
[12] Ehgoetz Martens KA, Lukasik EL, Georgiades MJ, Gilat M, Hall JM, Walton CC, Lewis SJG. Predicting the onset of freezing of gait: a longitudinal study. Mov Disord. 2018;33(1):128–35.
[13] Ou R, Wei Q, Cao B, Song W, Hou Y, Liu H, Yuan X, Zhao B, Wu Y, Shang H. Predictors of freezing of gait in Chinese patients with Parkinson’s disease. Brain Behav. 2018; 8(3): e00931.
[14] Banks SJ, Bayram E, Shan G, LaBelle DR, Bluett B. Non-motor predictors of freezing of gait in Parkinson’s disease. Gait Posture. 2019;68:311–6.
[15] Herman T, Shema S, Arie L, Giladi N, Hausdorff JM. Depressive symptoms may increase the risk of the future development of freezing of gait in patients with Parkinson’s disease: Findings from a 5-year prospective study. Parkinsonism Relat Disord. 2019; 60:98-104.
[16] Moreau C, et al. Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson’s disease. Brain. 2015; 138(5):1271–1283.
[17] Tekin I, Carkaci-Salli, N, Lewis MM, Mailman RB, Huang X, Vrana KE. The V81M variant of tyrosine hydroxylase is associated with more severe freezing of gait in Parkinson’s disease. Parkinsonism and Related Disorders. 2016; 23: 86–90.
To cite this abstract in AMA style:
B. Radojević, N. Dragašević-Mišković, A. Milovanović, M. Svetel, I. Petrović, I. Jančić, D. Stanisavljević, O. Milićević, M. Savić, V. Kostić. The correlation between genetic factors and freezing of gait in patients with Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/the-correlation-between-genetic-factors-and-freezing-of-gait-in-patients-with-parkinsons-disease/. Accessed November 21, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-correlation-between-genetic-factors-and-freezing-of-gait-in-patients-with-parkinsons-disease/