Jamra Rami Abou, Becker Tim, Klopp Norman, Dahdouh Faten, Schulze Thomas G, Gross Magdalena, Deschner Monika, Schmäl Christine, Illig Thomas, Rietschel Marcella, Propping Peter, Cichon Sven, Nöthen Markus M, Schumacher Johannes
Institute of Human Genetics, Department of Psychiatry, Life & Brain Center, University of Bonn, Bonn, Germany.
Psychiatr Genet. 2007 Feb;17(1):43-5. doi: 10.1097/YPG.0b013e32801118cd.
The alpha1/beta2/gamma2-containing heteropentamer is the most abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated as a susceptibility region for schizophrenia. Given this positional and functional evidence, Lo et al. (Mol Psychiatry 2004; 9: 603-608) performed systematic linkage disequilibrium mapping of the GABAAR gene cluster on 5q34 in 130 schizophrenic patients and 170 controls, all of Chinese Han origin. In the single locus and haplotype analyses, single nucleotide polymorphisms in the GABRB2 gene showed highly significant association. The estimated effect caused by GABRB2 varied between odds ratios of 2.27 and 5.12. In order to re-examine their findings, we analyzed the most significantly associated single nucleotide polymorphism in the GABRB2 gene in a sample of 367 patients with schizophrenia and 360 controls, all of German descent. Our sample had a sufficient power to detect the effects described. Neither single marker nor haplotype analysis revealed a significant association with the disease status. Thus, our results do not support the hypothesis that genetic variation at the GABRB2 locus plays a major role in schizophrenic patients of European descent and that such variation would explain the previously observed linkage findings at this chromosomal region.
含α1/β2/γ2的异五聚体是哺乳动物大脑中最丰富的γ-氨基丁酸A型受体亚型，其相应基因GABRA1、GABRB2和GABRG2基因位于染色体区域5q34，多项全基因组扫描表明该区域是精神分裂症的易感区域。基于这一位置和功能证据，Lo等人（《分子精神病学》2004年；9：603 - 608）对130名精神分裂症患者和170名对照（均为中国汉族血统）的5q34上的GABA A受体基因簇进行了系统的连锁不平衡图谱分析。在单基因座和单倍型分析中，GABRB2基因中的单核苷酸多态性显示出高度显著的关联。GABRB2引起的估计效应的比值比在2.27至5.12之间变化。为了重新检验他们的发现，我们在367名精神分裂症患者和360名对照（均为德国血统）的样本中分析了GABRB2基因中最显著相关的单核苷酸多态性。我们的样本有足够的检验效能来检测所描述的效应。单标记分析和单倍型分析均未显示与疾病状态有显著关联。因此，我们的结果不支持以下假设：GABRB2基因座的遗传变异在欧洲血统的精神分裂症患者中起主要作用，并且这种变异可以解释先前在该染色体区域观察到的连锁发现。
