Association of GRIN1 and GRIN2A-D With Schizophrenia and Genetic Interaction With Maternal Herpes Simplex Virus-2 Infection Affecting Disease Risk
Association of GRIN1 and GRIN2A-D With Schizophrenia and Genetic Interaction With Maternal Herpes Simplex Virus-2 Infection Affecting Disease Risk
复制标题
DOI：
10.1002/ajmg.b.31234
复制
发表时间：
2011-12-01
影响因子：
2.8
通讯作者：
Mortensen, Preben Bo
中科院分区：
文献类型：
--
作者：
Demontis, Ditte;Nyegaard, Mette;Mortensen, Preben Bo
n -甲基- d -天冬氨酸（NMDA）受体对大脑正常发育非常重要，多项证据支持NMDA受体功能低下参与精神分裂症的病理生理。因此，涉及编码NMDA受体的基因的基因变异和基因-环境相互作用可能影响精神分裂症的风险。本研究的目的是确定(1)编码NMDA受体的基因（GRIN1、GRIN2A、GRIN2B、GRIN2C和GRIN2D）的SNP变异是否与精神分裂症相关；(2)子代GRIN基因变异是否与母体妊娠期单纯疱疹病毒-2 （HSV-2）血清阳性相互作用，影响日后患精神分裂症的风险。来自三个独立收集的丹麦病例对照样本的个体进行了81个标签snp的基因分型（共984名诊断为精神分裂症的个体和1500名对照者），并在其中一个样本（365例病例和365例对照）中检测了抗母体HSV-2感染的抗体。GRIN2B中30个snp中有9个与精神分裂症显著相关。经Bonferroni校正后，1个SNP仍然显著（rs1806194, P-nominal = 0.0008）。7个snp （rs1805539, P-nominal = 0.0001）和2个snp （rs1806205, P-nominal = 0.0008）在子代HSV-2血清阳性与GRIN2B遗传变异之间存在显著交互作用。显著的关联和相互作用位于GRIN2B的3'区，提示该部分基因的遗传变异可能参与了精神分裂症的病理生理。(C) 2011 Wiley期刊公司
N-methyl-D-aspartate(NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, P-nominal = 0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, P-nominal = 0.0001 and rs1806205, P-nominal = 0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia. (C) 2011 Wiley Periodicals, Inc.