Abstract
ObjectiveDopaminergic 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.MethodsWe 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).ResultsMeta‐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%).ConclusionOur 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.
Highlights
Parkinson's disease (PD) is the second most common neurodegenera‐ tive disease after Alzheimer's disease.[1]
We hypothesized that dopaminergic neuronal degeneration seen in PD could result from a single nucleo‐ tide polymorphism (SNP) in the NMDA receptors (NMDARs)
Meta‐analysis results did not show a significant association between the rs4998386 polymorphism of the glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) gene and PD suscepti‐ bility when assuming an allelic model (OR, 0.90; 95% confidence intervals (CIs), 0.76‐1.07; P = .22; I2 = 53%), a dominant model (OR, 0.96; 95% CI, 0.82‐1.12; P = .62; I2 = 64%), or a recessive model (OR, 1.14; 95% CI, 0.93‐1.38; P = .22; I2 = 0%)
Summary
Parkinson's disease (PD) is the second most common neurodegenera‐ tive disease after Alzheimer's disease.[1]. Amantadine has been shown to noncompetitively block NMDARs at therapeutic concentrations in the central nervous system, supporting the association between NMDA and PD.[13] the precise role of NMDAR‐medi‐ ated excitotoxicity in PD progression has not been established and remains unclear. With this supporting data, we hypothesized that dopaminergic neuronal degeneration seen in PD could result from a single nucleo‐ tide polymorphism (SNP) in the NMDAR. Though these studies were not performed to establish association between GRIN2A rs4998386 SNP and PD, we extracted relevant data from these studies to perform a meta‐anal‐ ysis exploring the relationship between the rs4998386 SNP of the GRIN2A gene and PD susceptibility
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