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


CONCLUSIONS
This is a preliminary investigation with relatively small sample size.


CONCLUSIONS
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.
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.
Zuowei
Z
Wang
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. Electronic address: zhangchen645@gmail.com.
Chen
C
Zhang
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jia
J
Huang
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chengmei
C
Yuan
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wu
W
Hong
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jun
J
Chen
Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shunying
S
Yu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan, China.
Lin
L
Xu
Mood and Anxiety Clinic in the Mood Disorders Program of the Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, USA.
Keming
K
Gao
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yirufang@aliyun.com.
Yiru
Y
Fang
D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
D019208:Brain-Derived Neurotrophic Factor; C546087:MIRN206 microRNA, human; D035683:MicroRNAs
Bipolar disorders; Brain-derived neurotrophic factor; MiRNA-206; Mood stabilizer; Treatment response