微小RNA-206与脑源性神经营养因子基因在双相I型障碍中相互作用。

MiRNA-206 and BDNF genes interacted in bipolar I disorder.

作者信息

Wang Zuowei, Zhang Chen, Huang Jia, Yuan Chengmei, Hong Wu, Chen Jun, Yu Shunying, Xu Lin, Gao Keming, Fang Yiru

机构信息

Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Psychiatry, Division of Mood Disorders, Hongkou District Mental Health Center of Shanghai, Shanghai, China.

Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan, China.

出版信息

J Affect Disord. 2014 Jun;162:116-9. doi: 10.1016/j.jad.2014.03.047. Epub 2014 Apr 3.

DOI:10.1016/j.jad.2014.03.047

PMID:24767015

Abstract

BACKGROUND

Several lines of evidence have suggested that has-mir-206 (miRNA-206) may regulate brain-derived neurotrophic factor (BDNF) protein synthesis. The primary aim of this study was to determine whether miRNA-206 gene (MIR206) may confer susceptibility to bipolar disorder type I (BD-I) and treatment response to mood stabilizers. Also, we intended to verify the hypothesis that a potential interplay of MIR206 and BDNF may influence the genetic risk for BD-I and treatment response.

METHODS

The MIR206 rs16882131 and BDNF rs6265 polymorphisms were genotyped in 280 BD-I patients and 288 healthy controls. Treatment response to lithium and valproate was retrospectively determined.

RESULTS

No association was observed in the individual polymorphism with regards to risk of BD-I and treatment response. Our results showed a significant gene to gene interaction between the MIR206 rs16882131 and BDNF rs6265 polymorphisms that contribute to BD-I susceptibility and treatment response. Further analysis showed a significant interaction between MIR206 and BDNF on treatment score (F3, 138=8.61, P=0.046), and individuals with MIR206 T/T+TC and BDNF A/A genotypes had a significantly lower mean treatment score than those with MIR206 CC and BDNF A/A+A/G as well as those with MIR206 CC and BDNF G/G genotypes (P=0.018 and 0.013, respectively).

LIMITATION

This is a preliminary investigation with relatively small sample size.

CONCLUSION

Our findings provide initial evidence of the gene-to-gene interaction of MIR206 and BDNF in regards to the risk for BD-I as well as treatment response to mood stabilizers.

摘要

背景

多项证据表明，has-mir-206（miRNA-206）可能调节脑源性神经营养因子（BDNF）的蛋白质合成。本研究的主要目的是确定miRNA-206基因（MIR206）是否会增加I型双相情感障碍（BD-I）的易感性以及对心境稳定剂的治疗反应。此外，我们旨在验证MIR206和BDNF之间潜在的相互作用可能影响BD-I的遗传风险和治疗反应这一假设。

方法

对280例BD-I患者和288例健康对照进行MIR206 rs16882131和BDNF rs6265多态性基因分型。回顾性确定对锂盐和丙戊酸盐的治疗反应。

结果

未观察到个体多态性与BD-I风险和治疗反应之间的关联。我们的结果显示，MIR206 rs16882131和BDNF rs6265多态性之间存在显著的基因-基因相互作用，这与BD-I易感性和治疗反应有关。进一步分析显示，MIR206和BDNF在治疗评分上存在显著相互作用（F3, 138 = 8.61，P = 0.046），MIR206 T/T + TC和BDNF A/A基因型个体的平均治疗评分显著低于MIR206 CC和BDNF A/A + A/G基因型个体以及MIR206 CC和BDNF G/G基因型个体（分别为P = 0.018和0.013）。