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T-182C 多态性增强去甲肾上腺素转运体基因的启动子活性,但可能与抗抑郁反应无关。

The T-182C Polymorphism Enhances Promoter Activity of the Norepinephrine Transporter Gene, but may not be Associated with Antidepressant Response.

机构信息

Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, P.R. China.

Alzheimer's Disease Treatment Center, Shenyang Mental Health Center, Hunnan New District, Shenyang, P.R. China.

出版信息

Genet Test Mol Biomarkers. 2020 Dec;24(12):812-818. doi: 10.1089/gtmb.2020.0092. Epub 2020 Dec 7.

Abstract

Previous evidence has suggested that norepinephrine transporter () gene (solute carrier family 6, member 2 []) polymorphisms are involved in antidepressant response. Specifically, the polymorphism T-182C (rs2242446) located in the promoter region of has been found to be associated with antidepressant response in multiple ethnic backgrounds. However, the results are inconsistent. Moreover, few studies have focused on how this T-182C polymorphism might regulate promoter function. In this study, luciferase reporter assays were performed to examine the functional significance of the T-182C polymorphism. In addition, we performed a meta-analysis to explore whether this genetic variant is significantly involved in the antidepressant response. We found that the -182(T) allele significantly increased promoter function compared to the C allele based on luciferase reporter assays. For the meta-analysis, six articles were identified that explored the relationship between the T-182C polymorphisms and antidepressant response. This study revealed no significant association between these polymorphisms and response to antidepressants (OR = 1.23, 95% CI = 0.77 - 1.97,  = 0.38 for T-182C). The T-182C polymorphism enhances promoter activity, but may not be associated with antidepressant response.

摘要

先前的证据表明,去甲肾上腺素转运体()基因(溶质载体家族 6,成员 2 []) 多态性与抗抑郁反应有关。具体来说,位于启动子区域的 T-182C(rs2242446)多态性已被发现与多种种族背景下的抗抑郁反应相关。然而,结果并不一致。此外,很少有研究关注这种 T-182C 多态性如何调节 启动子功能。 在这项研究中,进行了荧光素酶报告基因检测,以检查 T-182C 多态性的功能意义。此外,我们进行了荟萃分析,以探讨这种遗传变异是否与抗抑郁反应显著相关。 我们发现,基于荧光素酶报告基因检测,-182(T) 等位基因与 C 等位基因相比,显著增加了启动子功能。对于荟萃分析,确定了六篇探讨 T-182C 多态性与抗抑郁反应之间关系的文章。这项研究表明,这些多态性与抗抑郁药物反应之间没有显著关联(OR = 1.23,95%CI = 0.77 - 1.97,  = 0.38 用于 T-182C)。 T-182C 多态性增强了启动子活性,但可能与抗抑郁反应无关。

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