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Neurotoxicity Research

, Volume 36, Issue 3, pp 463–471 | Cite as

Genetic Association Between NGFR, ADAM17 Gene Polymorphism, and Parkinson’s Disease in the Chinese Han Population

  • Wei-Wei Li
  • Ying-Ying Shen
  • Dong-Wan Chen
  • Hui-Yun Li
  • Qian-Qian Shi
  • Jing Mei
  • Heng Yang
  • Fa-Ying Zhou
  • An-Yu Shi
  • Tao Zhang
  • Xiu-Qing Yao
  • Zhi-Qiang Xu
  • Fan ZengEmail author
  • Yan-Jiang Wang
Original Article

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54–0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58–0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54–0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50–0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50–0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51–0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54–0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.

Keywords

NGFR ADAM17 Parkinson’s disease Gene polymorphism 

Notes

Funding Information

This study was supported by the National Natural Science Foundation of China (Grant no. 81870860 and 81571239) and the Ministry of Science and Technology of China (Grant no.2016YFC1306401).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_31_MOESM1_ESM.docx (20 kb)
Supplementary Table 1. (DOCX 19 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wei-Wei Li
    • 1
  • Ying-Ying Shen
    • 1
  • Dong-Wan Chen
    • 1
  • Hui-Yun Li
    • 1
  • Qian-Qian Shi
    • 1
  • Jing Mei
    • 1
  • Heng Yang
    • 1
  • Fa-Ying Zhou
    • 1
  • An-Yu Shi
    • 1
  • Tao Zhang
    • 1
  • Xiu-Qing Yao
    • 1
  • Zhi-Qiang Xu
    • 1
  • Fan Zeng
    • 1
    Email author
  • Yan-Jiang Wang
    • 1
  1. 1.Department of Neurology and Centre for Clinical Neuroscience, Daping HospitalThird Military Medical UniversityChongqingChina

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