Zuowei Wang1, Chen Zhang2, Jia Huang3, Chengmei Yuan3, Wu Hong3, Jun Chen3, Shunying Yu4, Lin Xu5, Keming Gao6, Yiru Fang7. 1. 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. 2. 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. 3. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 4. Department of Genetics, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan, China. 6. 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. 7. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yirufang@aliyun.com.
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.
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 MIR206rs16882131 and BDNFrs6265 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 MIR206rs16882131 and BDNFrs6265 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.
Authors: Madeline L Pfau; Immanuel Purushothaman; Jian Feng; Sam A Golden; Hossein Aleyasin; Zachary S Lorsch; Hannah M Cates; Meghan E Flanigan; Caroline Menard; Mitra Heshmati; Zichen Wang; Avi Ma'ayan; Li Shen; Georgia E Hodes; Scott J Russo Journal: Front Mol Neurosci Date: 2016-12-23 Impact factor: 5.639
Authors: Alessia Fiorentino; Niamh Louise O'Brien; Sally Isabel Sharp; David Curtis; Nicholas James Bass; Andrew McQuillin Journal: Bipolar Disord Date: 2016-11-16 Impact factor: 6.744
Authors: A J Forstner; A Hofmann; A Maaser; S Sumer; S Khudayberdiev; T W Mühleisen; M Leber; T G Schulze; J Strohmaier; F Degenhardt; J Treutlein; M Mattheisen; J Schumacher; R Breuer; S Meier; S Herms; P Hoffmann; A Lacour; S H Witt; A Reif; B Müller-Myhsok; S Lucae; W Maier; M Schwarz; H Vedder; J Kammerer-Ciernioch; A Pfennig; M Bauer; M Hautzinger; S Moebus; L Priebe; S Sivalingam; A Verhaert; H Schulz; P M Czerski; J Hauser; J Lissowska; N Szeszenia-Dabrowska; P Brennan; J D McKay; A Wright; P B Mitchell; J M Fullerton; P R Schofield; G W Montgomery; S E Medland; S D Gordon; N G Martin; V Krasnov; A Chuchalin; G Babadjanova; G Pantelejeva; L I Abramova; A S Tiganov; A Polonikov; E Khusnutdinova; M Alda; C Cruceanu; G A Rouleau; G Turecki; C Laprise; F Rivas; F Mayoral; M Kogevinas; M Grigoroiu-Serbanescu; P Propping; T Becker; M Rietschel; S Cichon; G Schratt; M M Nöthen Journal: Transl Psychiatry Date: 2015-11-10 Impact factor: 6.222