title: Significant linkage and association between a functional (GT)n polymorphism in promoter of the N-methyl-D-aspartate receptor subunit gene (GRIN2A) and schizophrenia.
abstract: Dysfunction of the N-methyl-d-aspartate (NMDA) type glutamate receptor has been proposed as a mechanism in the etiology of schizophrenia, based on the observation that non-competitive antagonists of the NMDA receptor, such as phencyclidine, induce schizophrenia-like symptoms. Previous study identified a variable (GT)n polymorphism in the promoter region of the N-methyl-d-aspartate (NMDA) subunit gene (GRIN2A), and showed its association with schizophrenia in a case-control study, together with a correlation between the length of the repeat and severity of chronic outcome. Our present study was aimed at confirming the association of the (GT)n polymorphism of GRIN2A promoter with schizophrenia using 122 Han Chinese sib-pair families. Non-parametric linkage analysis and transmission/disequilibrium test (TDT) were undertaken using the GENEHUNTER, v2.1. In non-parametric linkage analysis, suggestive linkage was found for the (GT)n polymorphism (NPL=2.77, P=0.002902). The TDT was significant for (GT)n polymorphism and that the (GT)23 was preferentially transmitted to schizophrenia-affected children (T/NT: 123:72, chi(2)=13.34, P=0.000260). Our results indicate that the (GT)n polymorphism in the promoter of GRIN2A gene may play a significant role in the etiology of schizophrenia among our samples.
authors.affiliation: Institute of Mental Health, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha Hunan 410011, PR China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Tang
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Chen
authors.forename: Xijia
authors.initials: X
authors.lastname: Xu
authors.forename: Renrong
authors.initials: R
authors.lastname: Wu
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002681:China / Q000453:epidemiology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D004247:DNA; D016194:Receptors, N-Methyl-D-Aspartate