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Polymorphism of neurodegeneration-related genes associated with Parkinson’s disease risk

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Abstract

Background

Neurodegenerative genes are critical in neuronal loss in Parkinson’s disease (PD). We performed a systematic meta-analysis including all the studies published on PD risk related to genes encoding enzymes vital for dopamine metabolism and neuron survival.

Methods

We included neurodegeneration-related genes which were divided into four groups according to their functions: main enzymes in dopamine metabolism, receptors and transporters for dopamine or other metabolites, neuroprotective factors for dopaminergic neurons, and genes associated with dopaminergic neurons survival reported in other neurological diseases. We collected original articles from PubMed, Embase, and Web of Science databases. Revman 5.3 software was used to analyze data. The allele model (AM) was used to test the effect size of the effect allele between the case group and the control group and secondary analysis using the dominant model (DM) and recessive model (RM) to analyze the contributions from heterozygote and homozygote to the allele risk. Odds ratio (OR) and 95% confidence interval (CI) were used to present the pooled results.

Results

We included 31 variants in 20 genes for the final pooled analysis. Consequently, SLC6A4/5-HTT HTTLPR, BDNF rs56164415, FGF20 rs1721100, PARK16 rs823128, rs823156, rs947211, APOE e2, A2M rs669, RIT2 rs12456492, MAPT intron 9 H1H2, and STH rs62063857 variants were statistically associated with PD risk while researched variants in COMT, DBH, MAO, DAT/SLC6A3, DRD2, GRIN2B, GSK3β, ATP13A2, LINGO1, PICALM, and GRN were not related to PD risk.

Conclusion

Several variants from neurodegeneration-related genes are associated with PD risk, which may help deepen the understanding of PD pathogenesis and improve clinical treatment strategies.

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Funding

This research was supported by the National Natural Science Foundation of China (No. 82001357), the Hunan Provincial Natural Science Foundation of China (No. 2020JJ5951, No. 2021JJ80079), the Youth Science Foundation of Xiangya Hospital (No. 2019Q17), the Degree & Postgraduate Education Reform Project of Central South University (No. 2021YJSKSA10), the Undergraduate Education Reform Project of Central South University (No. 2021CG065, No. 2021CG068) and the Research Project of Laboratory Construction and Management of Central South University (No. 202120).

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Author notes

  1. Jiaxin Li and Minhan Yi contributed equally to this work and are co-first authors.

Authors and Affiliations

  1. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Jiaxin Li, Minhan Yi, Binbin Li & Yuan Zhang

  2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Jiaxin Li, Minhan Yi, Binbin Li & Yuan Zhang

  3. Xiangya School of Medicine, Central South University, Changsha, China

    Jiaxin Li, Binbin Li & Shujuan Yin

  4. School of Life Sciences, Central South University, Changsha, Hunan, China

    Minhan Yi

  5. Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, China

    Ying Zhang

  6. Infection Control Center, Xiangya Hospital, Central South University, Changsha, China

    Ying Zhang

  7. Bangor College, Central South University of Forestry and Technology, Changsha, Hunan, China

    Zini Huang

  8. National Health Commission Key Laboratory for Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China

    Li Shu

Authors
  1. Jiaxin Li
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  2. Minhan Yi
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  3. Binbin Li
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  4. Shujuan Yin
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  5. Ying Zhang
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  6. Zini Huang
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  7. Li Shu
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  8. Yuan Zhang
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Contributions

Study design: M. H. Y. and Y. Z.; data collection: M. H. Y., J. X. L., B. B. L., S. J. Y., L. S., Y. Z., Z. N. H., and Y. Z.; data analysis: M. H. Y., J. X. L., B. B. L., S. J. Y., and Y. Z.; writing: M. H. Y., J. X. L., B. B. L., S. J. Y., L. S., and Y. Z.; funding: M. H. Y. and Y. Z.; administration: M. H. Y. and Y. Z.

Corresponding author

Correspondence to Yuan Zhang.

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Li, J., Yi, M., Li, B. et al. Polymorphism of neurodegeneration-related genes associated with Parkinson’s disease risk. Neurol Sci 43, 5301–5312 (2022). https://doi.org/10.1007/s10072-022-06192-8

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  • DOI: https://doi.org/10.1007/s10072-022-06192-8

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