Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul 23;2(3):174-183.
doi: 10.1002/agm2.12075. eCollection 2019 Sep.

Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene polymorphism (rs4998386) and Parkinson's disease susceptibility: A meta-analysis

Gaurav Nepal  1 , Jessica Holly Rehrig  2 , Rajeev Ojha  3
Affiliations

Glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene polymorphism (rs4998386) and Parkinson's disease susceptibility: A meta-analysis

Gaurav Nepal et al. Aging Med (Milton). .

Abstract

Objective: Dopaminergic neuronal degeneration seen in Parkinson's disease (PD) might result from a single nucleotide polymorphism (SNP) in the glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene. We thus performed a meta-analysis exploring the relationship between the rs4998386 SNP of the GRIN2A gene and PD susceptibility.

Methods: We searched PubMed, EMBASE, Web of Science, Google Scholar, and China National Knowledge Infrastructure for studies published between January 2005 and January 2019. The association between the rs4998386 polymorphism and PD susceptibility was evaluated by calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Meta-analysis results did not show a significant association between the rs4998386 polymorphism of the GRIN2A gene and PD susceptibility when assuming an allelic model (OR, 0.90; 95% CI, 0.76-1.07; P = .22; I 2 = 53%), a dominant model (OR, 0.96; 95% CI, 0.82-1.12; P = .62; I 2 = 64%), or a recessive model (OR, 1.14; 95% CI, 0.93-1.38; P = .22; I 2 = 0%).

Conclusion: Our meta-analysis found that the rs4998386 polymorphism of the GRIN2A gene is not associated with risk of PD in either Europeans or white Americans. However, large sample studies with different ethnicities should be conducted to establish the role of the rs4998386 polymorphism in PD pathophysiology.

Keywords: Excitotoxicity; NMDA receptor; Neurodegeneration; Parkinson's disease; glutamate ionotropic receptor NMDA type subunit 2A; rs4998386 polymorphism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow of systematic literature search and selection
Figure 2
Figure 2
Forest plot of the results for allelic model. CI, confidence interval; CPS‐IIN, Cancer Prevention Study II Nutrition Survey; HIHG, Hussman Institute for Human Genomics; HPFS, Health Professionals Follow‐up Study; NGRC, NeuroGenetics Research Consortium; NHS, Nurses’ Health Study; PAGE, Parkinson's, Genes, and Environment from the prospective NIH‐AARP Diet and Health Study; PEG, Parkinson, Environment and Gene
Figure 3
Figure 3
Forest plot of the results for recessive model. CI, confidence interval; CPS‐IIN, Cancer Prevention Study II Nutrition Survey; HIHG, Hussman Institute for Human Genomics; HPFS, Health Professionals Follow‐up Study; NGRC, NeuroGenetics Research Consortium; NHS, Nurses’ Health Study; PAGE, Parkinson's, Genes, and Environment from the prospective NIH‐AARP Diet and Health Study; PEG, Parkinson, Environment and Gene
Figure 4
Figure 4
Forest plot of the results for dominant model. CI, confidence interval; CPS‐IIN, Cancer Prevention Study II Nutrition Survey; HIHG, Hussman Institute for Human Genomics; HPFS, Health Professionals Follow‐up Study; NGRC, NeuroGenetics Research Consortium; NHS, Nurses’ Health Study; PAGE, Parkinson's, Genes, and Environment from the prospective NIH‐AARP Diet and Health Study; PEG, Parkinson, Environment and Gene
Figure 5
Figure 5
Funnel plot for detection of publication bias in allelic model
Figure 6
Figure 6
Funnel plot for detection of publication bias in recessive model
Figure 7
Figure 7
Funnel plot for detection of publication bias in dominant model
See this image and copyright information in PMC

References

    1. Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm. 2017;124:901‐905. - PubMed
    1. Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368‐376. - PubMed
    1. Ray Dorsey E, Elbaz A, Nichols E, et al. Global, regional, and national burden of Parkinson's disease, 1990‐2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939‐953. - PMC - PubMed
    1. Bekris LM, Mata IF, Zabetian CP. The genetics of Parkinson's disease. J Geriatr Psychiatry Neurol. 2010;23(4):228‐242. - PMC - PubMed
    1. Wider C, Wszolek ZK. Clinical genetics of Parkinson's disease and related disorders. Park Relat Disord. 2007;13(suppl 3):229‐232. - PubMed

LinkOut - more resources