IMR Press / JIN / Volume 20 / Issue 1 / DOI: 10.31083/j.jin.2021.01.366
Open Access Original Research
Thyrotroph embryonic factor polymorphism predicts faster progression of Parkinson’s disease in a longitudinal study
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1 Department of Neurology, Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Nanjing, 210029 Jiangsu Province, P. R. China
2 Department of Neurology, Shanghai East Hospital Affiliated to Tongji University, 150 Jimo Road, Pudong New Area, 201200 Shanghai, P. R. China
3 Department of Clinical Laboratory, Affiliated Brain Hospital of Nanjing Medical University, No. 264 Guangzhou Road, Nanjing, 210029 Jiangsu Province, P. R. China
*Correspondence: (Wei-Guo Liu)
J. Integr. Neurosci. 2021, 20(1), 95–101;
Submitted: 2 November 2020 | Revised: 10 December 2020 | Accepted: 12 January 2021 | Published: 30 March 2021
Copyright: © 2021 The Authors. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

The thyrotroph embryonic factor gene is a circadian clock-controlled gene. The rs738499 polymorphism of this gene has been suggested to be associated with depression and sleep disturbance in Parkinson’s disease in previous cross-sectional studies. We aimed to investigate whether this single nucleotide polymorphism is associated with the progression rates of various motor and non-motor symptoms in patients with Parkinson’s disease. We recruited 186 patients with Parkinson’s disease for a longitudinal study. Motor and non-motor symptoms were assessed at baseline and follow-up, and 170 Parkinson’s disease patients completed the clinical evaluation twice with an average follow-up period of 3.3 ± 1.1 years. A stepwise linear regression model was used to validate factors associated with Parkinson’s disease symptoms’ annual progression rates. Faster annual worsening rates of sleep quality and Hoehn-Yahr stage were found in carriers with the homozygous dominant (TT). After adjustment for related clinical factors, the rs738499 polymorphism showed a contribution of 3.1% to the annual decline rate on the Parkinson’s Disease Sleep Scale score and a contribution of 5.5% to the annual increase rate of the Hoehn-Yahr stage. Additionally, anxiety and axial symptoms predicted the progression of sleep disturbances and motor staging. The TT genotype of rs738499 might be a potential predictor of rapid deterioration in sleep quality and Hoehn-Yahr stage in patients with Parkinson’s disease and may advance the understanding of the genetic contributions to Parkinson’s disease.

Parkinson’s disease
Thyrotroph embryonic factor
Circadian genes
Longitudinal study
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