title: Polymorphisms in MicroRNA Genes And Genes Involving in NMDAR Signaling and Schizophrenia: A Case-Control Study in Chinese Han Population.
abstract: Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR-219/132/107 and 6 SNPs in 3'UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Fan
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Guang
authors.initials: G
authors.lastname: He
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Institution of Drug Clinical Trial, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Huafang
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
authors.forename: Shunying
authors.initials: S
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D035683:MicroRNAs; D016194:Receptors, N-Methyl-D-Aspartate; C548929:GRIN3A protein, human; C121001:NR2B NMDA receptor; C517662:CAMK2G protein, human