Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (<i>GRIN2B</i>) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

<div><p>Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (<i>GRIN2B</i>) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the <i>GRIN2B</i> gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (<i>χ²</i> = 8.425 and 4.994; <i>p</i> = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (<i>χ²</i> = 4.436; <i>p</i> = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (<i>χ²</i> = 11.162 and 38.204; <i>p</i> = 0.003 and 4.27×10^-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (<i>p</i> = 1.71×10^-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (<i>χ²</i> = 4.324, 4.582, and 4.492; <i>p</i> = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (<i>F</i> = 16.799, 7.112, and 13.357; <i>p</i> = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between <i>GRIN2B</i> polymorphisms and SZ susceptibility and symptoms in the Han Chinese population.</p></div

Haplotype block structure of the <i>GRIN2B</i> gene in both SZ patients and health controls.

<p>Thirty-four SNPs formed seven LD blocks. The index association SNP is represented by a diamond. The color of the remaining SNPs (circles) indicates LD with the index SNP based on pairwise r² values from our data.</p

Flow chart of participants through the study.

<p>Flow chart of participants through the study.</p

Comparison of serum prolactin levels between groups.

<p>Data are expressed as means ± SD and were analyzed by repeated measures analysis of variance or Student's t-test. *<i>P<</i>0.001, Aripiprazole group<i>vs</i>. control group for weeks 2–8;** <i>P</i><0.001, <i>vs</i>. control.</p

Adverse events observed in the study (incidence ≥5%).

<p>*Dystonia, muscle rigidity, oromandibular dystonia, parkinsonism, torticollis, and tremor.</p><p>Adverse events observed in the study (incidence ≥5%).</p

Changes in plasma glucose, Total cholesterol, Triglycerides,and High Density Lipoprotein after additional treatment aripiprazole.

<p>Values are mean ± SD.</p

Demographic and clinical characteristics of study participants.

<p>Values are mean ± SD.</p

Comparisons of BMIs (A) and plasma LDL levels (B) between groups.

<p>Data are expressed as means ± SD and were analyzed byStudent's t-test.*<i>P</i><0.05, <i>vs</i>. control.</p