Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case–control study

Hyperactivation of N-methyl- d-aspartate receptors (NMDARs) leads to neuronal excitotoxicity and is suggested to play a role in many brain disorders, including Alzheimer's disease and schizophrenia. However, the association between polymorphisms in the genes that code for NMDAR subunits, N-methyl- d-aspartate 1 and 2B ( GRIN1 and GRIN2B) and Parkinson's disease (PD) remains unclear. In a hospital-based case–control study of PD, DNA samples were collected from 101 PD patients and 205 healthy controls. Genotyping assays were used to screen for polymorphisms in the GRIN1 (rs2301364 T > C, rs28489906 T > C, and rs4880213 T > C) and GRIN2B ( C366G, C2664T, and rs1805476 T > G) genes, and logistic regression analysis was then used to assess the association between these single nucleotide polymorphisms (SNPs) and PD susceptibility. None of the 6 SNPs were significantly associated with PD risk on their own. However, in conjunction with putative low-risk genotypes for the GRIN1 gene, the GRIN2B C366G variant was significantly associated with reduced PD risk compared with the homozygous genotype 366CC (OR = 0.38, 95%CI = 0.17–0.93, P = 0.033). A synergistic effect on risk reduction was observed in subjects who carried multiple polymorphisms of GRIN1 and the GRIN2B C366G polymorphism (OR = 0.78, 95%CI = 0.59–1.02, P trend = 0.073). Our results suggest that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.