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

Abstract

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 (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B 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 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 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 (χ2 = 4.324, 4.582, and 4.492; p = 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 (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between GRIN2B polymorphisms and SZ susceptibility and symptoms in the Han Chinese population.

Comparative Study on Serum Levels of 10 Trace Elements in Schizophrenia

“…However, some study did not find any association between antipsychotic doses, duration of illness, and smoking status, and the changes of several trace elements, including manganese, selenium, iron, copper and zinc [ 17 ]. In addition, even if the socioeconomic and nutritional status of cases and controls are similar, it is still impossible to rule out the possibility that various genetic profiles might play a role in the schizophrenia risk [ 38 ].…”

Association between cerebral dopamine neurotrophic factor (CDNF) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population

“…Stage 1 samples were those from our previous publications [ 16 , 17 ], and included 528 paranoid SZ patients (mean age: 27.32 ± 8.03 years old) and 528 healthy controls (mean age: 27.73 ± 8.01 years old) who were recruited from March 2005 to December 2008. Stage 2 samples included 142 SZ patients (paranoid, n = 122 and undifferentiated, n = 20; mean age: 29.28 ± 7.17 years old) and 173 healthy controls (mean age: 32.49 ± 7.43 years old) who were recruited from May 2011 to December 2014.…”

“…SZ was diagnosed as previously described [ 16 , 17 ] according to the criteria listed in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV). Exclusion criteria were as follows: patients had been diagnosed with other psychiatric disorders; or had organic brain disease, substance dependence, severe medical complications, or neurological diseases.…”

“…A total of 372 SZ patients (stage 1, n = 229 and stage 2, n = 143) who were not taking antipsychotic medications were evaluated for psychotic syndromes using the PANSS [ 19 ]. Inclusion and exclusion criteria for healthy controls were as described our previous papers [ 16 , 17 ]. These subjects were screened by psychiatrists in simple non-structured interviews.…”

The association between the GRIN2B gene and verbal fluency and impairment of abstract thinking in schizophrenia

“…цептора, в частности гена GRIN2B, кодирующего субъединицу NR2B. Его связь с отдельными симптомами шизофрении пока остается малоизученной [8]. Однако обнаружены ассоциации полиморфных локусов в этом гене с риском развития шизофрении [9][10][11] и выявляемыми при психологическом исследовании нарушениями вербального мышления больных [12].…”