Vilella Elisabet, Costas Javier, Sanjuan Julio, Guitart Míriam, De Diego Yolanda, Carracedo Angel, Martorell Lourdes, Valero Joaquín, Labad Antonio, De Frutos Rosa, Nájera Carmen, Moltó M Dolores, Toirac Ivette, Guillamat Roser, Brunet Anna, Vallès Vicenç, Pérez Lucía, Leon Melquíades, de Fonseca Fernando Rodríguez, Phillips Christopher, Torres María
Faculty of Medicine, Rovira i Virgili University, Reus, Spain.
J Psychiatr Res. 2008 Mar;42(4):278-88. doi: 10.1016/j.jpsychires.2007.02.005. Epub 2007 Apr 3.
Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.
近期报告显示，DAO、DAOA、DTNBP1、NRG1和RGS4是一些在精神分裂症易感性方面最常被重复验证的基因。此外，这些基因的功能可能汇聚于谷氨酸代谢的共同通路。本研究的目的是评估这些基因中的每一个，或它们之间的相互作用，是否与精神分裂症相关。对589名被诊断为精神分裂症的西班牙患者进行了病例对照研究，并与617名同等的对照对象进行比较。在所有个体中确定了每个基因中的几个单核苷酸多态性（SNP）。比较了病例组和对照组之间的SNP和单倍型频率。通过多因素降维（MDR）方法分析了同一基因座或不同基因座上不同SNP之间的相互作用。我们在DTNBP1基因的内含子VII中发现了新的精神分裂症风险和保护性单倍型；DTNBP1是迄今为止该疾病最重要的候选基因之一。然而，未发现DAO、DAOA、NRG1和RGS4与精神分裂症之间存在关联。本研究未证实这五个基因之间的基因-基因相互作用会增加该疾病风险的假设。总之，这些结果可能为精神分裂症与失调结合蛋白基因（DTNBP1）之间的关联提供进一步支持，但不能证明该疾病与DAO、DAOA、NRG1和RGS4之间存在关联，也不能证明与这些基因的相互作用有关。鉴于最近的数据，这些结果需要谨慎解释，有待未来使用密集遗传图谱进行分析。
