TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis
TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis
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DOI：
10.1016/j.schres.2013.10.038
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发表时间：
2014-01-01
影响因子：
4.5
通讯作者：
Joober, Ridha
中科院分区：
文献类型：
--
作者：
Albanna, Ammar;Choudhry, Zia;Joober, Ridha
背景：在全基因组关联研究中，TCF4 基因的单核苷酸多态性一直与精神分裂症相关，包括 rs9960767 的 C 等位基因。然而，其在调节精神分裂症表型中的确切作用尚不清楚。目的：全面探讨TCF4的rs9960767风险等位基因(C)与首发精神病(FEP)患者认知表现之间的关系。方法：对173例FEP患者进行全面的神经认知评估，并对rs9960767进行基因分型。使用协方差 MANCOVA 多变量分析将风险等位基因 (CA/CC) 携带者与非携带者 (AA) 进行比较。种族、阴性症状和药物滥用被列为协变量。结果：与非携带者相比，风险等位基因携带者在推理/解决问题的认知领域的表现显着较低（F-1、F-172 = 4.4，p = .038）。对其他认知领域或一般认知没有显着的基因型影响。即使在控制智商时，这种对推理/问题解决领域的影响仍然显着 (F-1,F-172 = 4.3, p = .039)。结论：TCF4 的 rs9960767 (C) 似乎与 FEP 患者推理/问题解决认知领域的神经认知缺陷相关。需要在更大的样本中确认这一发现并包括其他 TCF4 多态性，以获得该结果的进一步有效性。 (C) 2013 Elsevier B.V. 保留所有权利。
Background: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known.Aims: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP).Methods: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates.Results: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F-1,F-172 = 4.4, p = .038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F-1,F-172 = 4.3, p = .039).Conclusions: rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result. (C) 2013 Elsevier B.V. All rights reserved.