Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Department of Child & Adolescent Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.
Psychiatry Res. 2017 Jun;252:201-207. doi: 10.1016/j.psychres.2017.03.013. Epub 2017 Mar 7.
The gene D-amino acid oxidase activator (DAOA), which has a former name of G72, and the D-amino acid oxidase (DAO) gene have been suggested as candidate genes of schizophrenia. However, association studies have so far yielded equivocal results. We analyzed one single nucleotide polymorphism (SNP) for DAO (rs3741775) and seven SNPs for G72 (rs3916956, rs2391191, rs9558562, rs947267, rs778292, rs3918342, and rs1421292) in this study enrolling 248 schizophrenia cases and 267 controls in the Taiwanese samples. In SNP-based single locus association analyses, the rs778292 in the DAOA gene showed significant association with schizophrenia. The rs3741775 in the DAO gene could not withstand statistically significant after multiple corrections. Additionally, a three-SNP haplotype (rs778292-rs3918342-rs1421292) in the DAOA gene were observed to be significantly associated with schizophrenia. Among them, the TCT haplotype presented higher prevalence in controls than in cases whereas the TTT and CTT haplotype were significantly more frequent in cases than in controls. The study also provides significant evidence for epistatic interactions among DAOA and DAO gene in the development of schizophrenia. These results provide additional evidence and indicate that the DAOA gene and DAOA-DAO gene-gene interactions might play a role for schizophrenia in a Taiwanese sample.
该基因 D-氨基酸氧化酶激活剂 (DAOA),原名 G72,以及 D-氨基酸氧化酶 (DAO) 基因被认为是精神分裂症的候选基因。然而,关联研究迄今为止产生了模棱两可的结果。我们分析了 DAO 的一个单核苷酸多态性(rs3741775)和 G72 的七个单核苷酸多态性(rs3916956、rs2391191、rs9558562、rs947267、rs778292、rs3918342 和 rs1421292),共纳入 248 例精神分裂症病例和 267 例对照组,这些病例和对照组均来自台湾样本。在基于 SNP 的单基因座关联分析中,DAOA 基因中的 rs778292 与精神分裂症显著相关。DAO 基因中的 rs3741775 在经过多次校正后无法承受统计学上的显著差异。此外,DAOA 基因中的一个三 SNP 单倍型(rs778292-rs3918342-rs1421292) 与精神分裂症显著相关。其中,TCT 单倍型在对照组中的出现频率高于病例组,而 TTT 和 CTT 单倍型在病例组中的出现频率明显高于对照组。该研究还提供了 DAOA 和 DAO 基因在精神分裂症发病机制中存在上位性相互作用的重要证据。这些结果提供了额外的证据,并表明 DAOA 基因和 DAOA-DAO 基因-基因相互作用可能在台湾样本中对精神分裂症起作用。