DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy
DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy
复制标题
DOI：
10.1016/j.jad.2014.06.048
复制
发表时间：
2014-10-15
影响因子：
6.6
通讯作者：
Fananas, Lourdes
中科院分区：
文献类型：
--
作者：
Arias, Barbara;Fabbri, Chiara;Fananas, Lourdes
背景：重性抑郁障碍（MDD）是一种常见病，发病率高，治疗效果不理想。遗传多态性对MOD的发病机制和抗抑郁作用有很大影响。在有希望的候选基因中，精神分裂症1型（DISCI）、translin-associated factor X（TSNAX）和D-氨基酸氧化酶激活剂（DADA）在神经发育、神经可塑性和神经传递中起调节作用，并与主要精神疾病有交叉关系。本文通过病例对照研究了已报道基因中的13个SNPs在MDD易感性中的作用（分别为n=320和n=150）研究和西酞普兰疗效（n=157）。西酞普兰疗效指标为反应（第4周）和缓解（第12周）。结果：发现rs3738401（DISCI）、1615409和rs766288（TSNAX）与MOD之间存在关联的证据（分别为p=0.004、p=0.0019和p=0.008）。检测到缓解与DISCI rs 821616和DADA rs778294之间的关联趋势，并通过重复测量ANOVA（p=0.0008）确认rs778294。在星星 *D的单核苷酸多态性从20至40 Kbp的DISCI结果在原始样本中的集群与西酞普兰的反应，以及rs778330（12,325 bp角rs778294）。局限性：相对较小的原始样本的大小，并集中在只有三个候选genes.Conclusions：本研究支持DISC 1-TSNAX变体在MOD易感性的作用。另一方面，DADA rs778294和DISCI rs6675281-rs 1000731周围的遗传区域可能影响西酞普兰的疗效。(C)2014爱思唯尔有限公司版权所有。
Background: Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MOD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISCI), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DADA) were suggested since their regulator role in neurodevelopment, neuroplaslicity and neurotransmission, and previous evidence of cross involvement in major psychiatric diseases.Methods: The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR*D genome-wide dataset (n=1892) for replication.Results: Evidence of association among rs3738401 (DISCI), is 1615409 and rs766288 (TSNAX) and MOD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISCI rs821616 and DADA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR*D a cluster of SNPs from 20 to 40 Kbp from DISCI findings in the original sample was associated with citalopram response, as well as rs778330 (12,325 bp horn rs778294).Limitations: Relatively small size of the original sample and focus on only three candidate genes.Conclusions: The present study supported a role of DISC1-TSNAX variants in MOD susceptibility. On the other hand, genetic regions around DADA rs778294 and DISCI rs6675281-rs1000731 may influence citalopram efficacy. (C) 2014 Elsevier B.V. All rights reserved.