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

Gaurav Nepal; Jessica Holly Rehrig; Rajeev Ojha

doi:10.1002/agm2.12075

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

Aging Med (Milton). 2019 Jul 23;2(3):174-183. doi: 10.1002/agm2.12075. eCollection 2019 Sep.

Authors

Gaurav Nepal¹, Jessica Holly Rehrig², Rajeev Ojha³

Affiliations

¹ Tribhuvan University Institute of Medicine Kathmandu Nepal.
² University of New England College of Osteopathic Medicine Biddeford Maine USA.
³ Department of Neurology Tribhuvan University Institute of Medicine Kathmandu Nepal.

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.