Genetic variation in N-methyl-D-aspartate receptor subunit NR3A but not NR3B influences susceptibility to Alzheimer's disease.
BACKGROUND
The administration of memantine, an N-methyl-D-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.


OBJECTIVE
The potential association of polymorphisms in NMDA receptor subunits NR3A and NR3B, encoded by the GRIN3A and GRIN3B genes, with AD was investigated.


METHODS
We performed a case-control study. Two single nucleotide polymorphisms, 3104 G/A (rs10989563) and 3723 G/A (rs3739722), in the GRIN3A gene and 2 GRIN3B gene polymorphisms, 1210 C/T (rs4807399) and 1730 C/T (rs2240158), were studied.


RESULTS
Upon genotyping of the exonic polymorphism in the GRIN3A gene, 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 GRIN3B gene variants 1210 C/T and 1730 C/T analyzed, no strong association with AD was observed.


CONCLUSIONS
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.
Liu
Hsin-Ping
HP
Graduate Institute of Acupuncture Science, Asia University, Taichung, Taiwan, ROC.
Lin
Wei-Yong
WY
Liu
Shu-Hsiang
SH
Wang
Wen-Fu
WF
Tsai
Chon-Haw
CH
Wu
Bor-Tsang
BT
Wang
Chien-Kuo
CK
Tsai
Fuu-Jen
FJ
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D005819:Genetic Markers; C464437:NR3A NMDA receptor; C501155:NR3B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D004247:DNA