Evaluation of the role of FMR1 CGG repeat allele in Parkinson's disease from the Chinese population

Juan Chen; Yuwen Zhao; Xun Zhou; Jin Xue; Qiao Xiao; Hongxu Pan; Xiaoxia Zhou; Yaqin Xiang; Jian Li; Liping Zhu; Zhou Zhou; Yang Yang; Qian Xu; Qiying Sun; Xinxiang Yan; Jieqiong Tan; Jinchen Li; Jifeng Guo; Ranhui Duan; Beisha Tang; Qiao Yu; Zhenhua Liu

doi:10.3389/fnagi.2023.1234027

Evaluation of the role of FMR1 CGG repeat allele in Parkinson's disease from the Chinese population

Front Aging Neurosci. 2023 Jul 31:15:1234027. doi: 10.3389/fnagi.2023.1234027. eCollection 2023.

Authors

Juan Chen^#^{1

2}, Yuwen Zhao^#^{1

2}, Xun Zhou³, Jin Xue⁴, Qiao Xiao⁴, Hongxu Pan¹, Xiaoxia Zhou¹, Yaqin Xiang¹, Jian Li⁵, Liping Zhu⁶, Zhou Zhou³, Yang Yang¹, Qian Xu¹, Qiying Sun³, Xinxiang Yan¹, Jieqiong Tan⁴, Jinchen Li^{2

3

4}, Jifeng Guo^{1

2

4

7}, Ranhui Duan⁴, Beisha Tang^{1

2

4

7}, Qiao Yu³, Zhenhua Liu^{1

2

4

7}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Bioinformatics Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Centre for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
⁵ Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
⁷ Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China.

^# Contributed equally.

Abstract

Objective: There is controversial evidence that FMR1 premutation or "gray zone" (GZ) allele (small CGG expansion, 45-54 repeats) was associated with Parkinson's disease (PD). We aimed to explore further the association between FMR1 CGG repeat expansions and PD in a large sample of Chinese origin.

Methods: We included a cohort of 2,362 PD patients and 1,072 controls from the Parkinson's Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) in this study and conducted repeat-primed polymerase chain reaction (RP-PCR) for the size of FMR1 CGG repeat expansions.

Results: Two PD patients were detected with FMR1 premutation (61 and 56 repeats), and the other eleven PD patients were detected with the GZ allele of FMR1 CGG repeat expansions. Those thirteen PD patients responded well to levodopa and were diagnosed with clinically established PD. Specifically, one female PD patient with GZ allele was also found with premature ovarian failure. However, compared to healthy controls, we found no significant enrichment of GZ allele carriers in PD patients or other subgroups of PD cases, including the subgroups of female, male, early-onset, and late-onset PD patients. Furthermore, we did not find any correlation between the FMR1 gene CGG repeat sizes and age at onset of PD.

Conclusion: It suggested that FMR1 premutation was related to PD, but the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in PD cases of Chinese origin. Further larger multiple ethnic studies are needed to determine further the role of the FMR1 GZ allele in PD.

Keywords: CGG repeat; FMR1 gene; Parkinson’s disease; gray zone; premutation.

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. U20A20355, 82001359, and 82001358), the Hunan Provincial Natural Science Foundation of China (Grant Nos. 2022JJ40803, 2021JJ41046, and 2023JJ41023), the Hunan Innovative Province Construction Project (Grant Nos. 2019SK2335 and 2021SK1010), the Scientific Research Project of Hunan Provincial Health Commission (Grant No. 202203074637), the National Key Research and Development Program of China (Grant No. 2021YFC2501204), and the Youth Science Foundation of Xiangya Hospital (No. 2022Q11).