Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia.
Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia.
复制标题
DOI：
10.1038/ejhg.2014.261
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
SLC 1A 2基因编码兴奋性氨基酸转运蛋白2（EAAT 2）。谷氨酸是兴奋性神经传递的主要介质，EAAT 2负责从突触间隙清除神经递质。SLC 1A 2的遗传变异与一系列神经和神经精神疾病有关，包括精神分裂症（SZ）、自闭症和双相情感障碍（BD）的核心表型。对1099例或32例BD患者的SLC 1A 2基因编码区和调控区进行高分辨熔解或测序。在SLC 1A 2基因中检测到32种变异。在1099份BD和1095份对照样本中选择了15种潜在的病因学变异体进行基因分型。还对630名患有SZ的参与者进行了5种氨基酸改变变体的基因分型。没有发现任何变异与BD或SZ或两种疾病的结合有关。然而，两个经常性的错义变体（rs 145827578：G>A，p. (G6S); A，p.（R31 Q）和一个重复性5′-非翻译区（UTR）变异（ss 825678885：G>T）。对仅复发病例错义变异和仅病例错义及5′-UTR变异的联合分析显示与合并疾病相关的名义证据（Fisher's P=0.019和0.0076）。这些发现本质上是探索性的，并等待在更大的队列中复制，然而，它们提供了有趣的证据，即SLC 1A 2基因中潜在的功能性罕见变异可能赋予精神障碍的易感性。
The SLC1A2 gene encodes the excitatory amino acid transporter 2 (EAAT2). Glutamate is the major mediator of excitatory neurotransmission and EAAT2 is responsible for clearing the neurotransmitter from the synaptic cleft. Genetic variation in SLC1A2 has been implicated in a range of neurological and neuropsychiatric conditions including schizophrenia (SZ), autism and in core phenotypes of bipolar disorder (BD). The coding and putative regulatory regions of SLC1A2 gene were screened for variants using high resolution melting or sequenced in 1099 or in 32 BD subjects. Thirty-two variants were detected in the SLC1A2 gene. Fifteen potentially etiological variants were selected for genotyping in 1099 BD and 1095 control samples. Five amino acid changing variants were also genotyped in 630 participants suffering from SZ. None of the variants were found to be associated with BD or SZ or with the two diseases combined. However, two recurrent missense variants (rs145827578:G>A, p.(G6S); rs199599866:G>A, p.(R31Q)) and one recurrent 5′-untranslated region (UTR) variant (ss825678885:G>T) were detected in cases only. Combined analysis of the recurrent-case-only missense variants and of the case-only missense and 5′-UTR variants showed nominal evidence for association with the combined diseases (Fisher's P=0.019 and 0.0076). These findings are exploratory in nature and await replication in larger cohorts, however, they provide intriguing evidence that potentially functional rare variants in the SLC1A2 gene may confer susceptibility to psychotic disorders.
登录
查看更多内容
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Bauer, Deborah;Haroutunian, Vahram;Meador-Woodruff, James H.;McCullumsmith, Robert E.
通讯作者：
McCullumsmith, Robert E.
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
poly（a）结合蛋白：用于基因表达的转录后控制的多功能支架。
影响因子：
12.3
作者：
Mangus, David A;Evans, Matthew C;Jacobson, Allan
通讯作者：
Jacobson, Allan
影响因子：
14.9
作者：
Barreau C;Paillard L;Osborne HB
通讯作者：
Osborne HB