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

[[abstract]]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. Aim: 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. Conclusion: 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. Copyright (C) 2009 S. Karger AG, Base

A Novel Genetic Variant of BMP2K Contributes to High Myopia

[[abstract]]Loss of eye growth regulation may cause myopia, because modulation of optic globe size is essential for the generation of normal optic power. Evidence has implied variations of BMP2 gene expression mediate ocular development and retinal tissue remodeling. Given BMP2 as a potential regulator involved in myopia development, we investigate whether gene BMP2-inducible kinase (BMP2K, BIKe), whose expression is up-regulated during BMP2-induced osteoblast differentiation, contributes to susceptibility of high myopia. Participants grouped into high myopia had a spherical equivalent greater than -6.00 D, compared with a control group of spherical equivalent less than -0.5 D. Genotyping of polymorphisms 1379 G/A (rs2288255) and 3171 C/G (rs-12507099), corresponding with 405 Gly/Ser and 1002 Thr/Ser variation in the BMP2K gene were determined by PCR-restriction fragment length polymorphism and associative study performed by comparing high myopic subjects and healthy controls. The frequency of A allele in the BMP2K gene 1379 G/A polymorphism showed a significant difference between cases and controls (P<0.001, OR = 2.99, 95% CI = 1.62-5.54) and subjects with either AA or AG genotype show higher risk than GG genotype (P<0.001, OR = 3.07, 95% CI = 1.59-5.92), while 3171 C/G polymorphism was not significant from this survey. These data suggest that BMP2K gene 1379 G/A variant is strongly correlated with high myopia and may contribute to a genetic risk factor for high degrees of myopic pathogenesis. J. Clin. Lab. Anal. 23:362-367, 2009. (C) 2009 Wiley-Liss, Inc