PARK2 and PARK7 Gene Polymorphisms as Risk Factors Associated with Serum Element Concentrations and Clinical Symptoms of Parkinson’s Disease

Abstract

Besides clinical and imaging techniques, there is a lack of molecular makers for the diagnosis of Parkinson’s disease (PD). There is an immense need to develop biomarkers associated with the phenotypes which may be valuable for individualized treatment. Single-nucleotide polymorphisms (PARK2: Ser167Asn (G>A) and Val380Leu (G>C); PARK7: IVS4 + 46G>A and IVS4 + 30T>G) in PD-related genes were examined to elucidate its relationship with concentration of serum elements and clinical symptoms of PD. A total of 214 PD patients and 213 controls from Indian population were genotyped using PCR and DNA sequencing methods. The serum element concentrations were detected and clinical symptoms were determined based on UPDRS scale and recorded at the time of sample collection. The IVS4 + 30T>G, Ser167Asn (G>A) and Val380Leu (G>C) polymorphisms appeared to alter element concentrations in PD. The patients with Ser167Asn polymorphism showed significant association with copper, iron and zinc that reinforces the role of A allele as a factor for change in the concentrations of elements, than those patients with G allele. In particular, patients with A allele of Ser167Asn have risk of having high serum iron concentration (OR 11.55, 95% CI 5.59–23.85), which are associated with dementia and postural imbalance. Similar results were observed for Val380Leu (G>C) and IVS4 + 30T>G polymorphisms which suggest their role in element concentration and neurological symptoms. Overall, our study demonstrates the influence of polymorphisms of PD genes on element concentrations and clinical symptoms. Results of this study may be taken into account when considering the contributing factors for PD symptoms.

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Acknowledgements

This research work is supported by the Grant (Project Sanction No: 4-FP/6/PMI (Considered under National project “Human Origins, Genome and People of India-DNA Polymorphism”)) from Anthropological Survey of India, Ministry of Culture, Government of India and ICMR EMS Grant to VRR (Letter No. 74/1/2016-Pers.EMS). We are thankful to the team of doctors, the PD patients and control subjects for voluntarily taking part in this research work and donating their blood samples. We also thank Mitali Maity (nurse in NNC) for helping in the collection of blood samples from the OPD of NNC. JS is thankful to CSIR for providing the Research Associate Fellowship (CSIR RA Code ID: 9/45(1283)/2013 EMR-I).

Funding

This research work is supported by the Grant (Project Sanction No: 4-FP/6/PMI (Considered under National project “Human Origins, Genome and People of India-DNA Polymorphism”)) from Anthropological Survey of India, Ministry of Culture, Government of India and ICMR EMS grant to VRR (Letter No 74/1/2016-Pers.EMS).

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JS designed the research work with VRR and SSSJA, performed the experiments and wrote the manuscript. SSSJA planned the research work, statistically analysed the data and wrote the draft of the manuscript. AA was involved in the statistical analysis. R provided critical suggestion for the genetic analysis. RM provided critical suggestion while analysing the data. TKB and GG are the clinical collaborators involved in identifying the PD patients and control. VRR organized the research project, mentor, who received the grant for the project on PD in India.

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Correspondence to S. S. J. Shiek Ahmed or Vadlamudi Raghavendra Rao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Sanyal, J., Anirudhan, A., Banerjee, T.K. et al. PARK2 and PARK7 Gene Polymorphisms as Risk Factors Associated with Serum Element Concentrations and Clinical Symptoms of Parkinson’s Disease. Cell Mol Neurobiol 40, 357–367 (2020). https://doi.org/10.1007/s10571-019-00734-z

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Keywords

  • Serum trace element
  • Metal imbalance
  • Parkinson’s disease
  • Gene polymorphisms