Genetic Variation in N-Methyl-D-Aspartate Receptor Subunit NR3A but Not NR3B Influences Susceptibility to Alzheimer’s Disease

<i>Background:</i> The administration of memantine, an N-methyl-<i>D</i>-aspartate (NMDA) receptor antagonist, has clinically improved the cognitive function of patients with Alzheimer’s disease (AD), indicating that a disturbance in glutamatergic transmission might be involved in a predisposition to developing the disease. <i>Aim:</i> The potential association of polymorphisms in NMDA receptor subunits NR3A and NR3B, encoded by the <i>GRIN3A</i> and<i> GRIN3B</i> genes, with AD was investigated. <i>Methods:</i> We performed a case-control study. Two single nucleotide polymorphisms, 3104 G/A (rs10989563) and 3723 G/A (rs3739722), in the <i>GRIN3A</i> gene and 2 <i>GRIN3B</i> gene polymorphisms, 1210 C/T (rs4807399) and 1730 C/T (rs2240158), were studied. <i>Results:</i> Upon genotyping of the exonic polymorphism in the <i>GRIN3A</i> gene<i>,</i> the G allele was present at a higher rate than the A allele at position 3723 in AD patients compared with normal groups (p < 0.05). Three haplotypes (designated Ht1–3) were identified from these 2 polymorphisms (3104 G/A and 3723 G/A), and the distribution of Ht2 (AG) differed between AD patients and controls (p < 0.05). Additionally, from the 2 <i>GRIN3B</i> gene variants 1210 C/T and 1730 C/T analyzed, no strong association with AD was observed. <i>Conclusion:</i> These observations suggest that the genetic variation of the NR3A, but not NR3B, subunit of the NMDA receptor may be a risk factor for AD pathogenesis among the Taiwanese population.