title: Correlation of functional GRIN2A gene promoter polymorphisms with schizophrenia and serum D-serine levels.
abstract: Schizophrenia is a severe, complex mental disorder. Abnormal glutamate neurotransmission mediated by decreased expression of N-methyl-d-aspartic acid receptors (NMDArs) and its endogenous co-agonist d-serine (d-Ser) has been proposed as one of the hypotheses of the pathogenesis of schizophrenia. GRIN2A gene promoter polymorphism causes changes in the regulation of the expression of NMDAr subunit genes. Our study is aimed at evaluating a possible association between GRIN2A promoter GT polymorphisms and schizophrenia in the Han Chinese population in Shaanxi and the relationship between serum d-Ser levels and GRIN2A (GT)n in schizophrenia. Four hundred and twenty patients with schizophrenia and 410 healthy individuals were recruited in this study and GRIN2A (GT)n repeats as well as serum d-Ser levels were measured in all of the subjects. Nineteen alleles were found in (GT)n locus. The allele frequency of (GT)21, (GT)22 and (GT)23 in schizophrenic subjects was significantly lower compared with the mentally healthy controls, while the allele (GT)26 was significantly more frequent than in normal persons. Transcriptional activity of GRIN2A promoter was gradually suppressed with the increase in the length of the (GT)n repeats. d-Ser levels in the serum of the GRIN2A (GT)21 schizophrenic patients were significantly lower than those of the GRIN2A (GT)21 healthy control. A significant correlation between serum d-Ser levels and GRIN2A (GT)21 in schizophrenia was detected. GRIN2A (GT)21 may play a significant role in the etiology of schizophrenia among the Chinese Han population of Shaanxi.
authors.affiliation: Department of Physiotherapy & Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Xi'an Mental Health Center, Xi'an 710061, Shaanxi, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dang
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Physiotherapy & Rehabilitation, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address: zhaohui_liuxa@163.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, PR China. Electronic address: kaijiaofumm@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiao
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood / Q000235:genetics*; D012694:Serine / Q000097:blood*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine
keywords: GRIN2A; GT; Schizophrenia; Single nucleotide polymorphism; d-Serine