Interaction between COMT and MTHFR genetic variants protect against risk for bipolar II disorder in Han Chinese

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Liang-Jen Wang, Sheng-Yu Lee, Yun-Hsuan Chang and Ru-Band Lu

Chang Gung University, Taiwan

Kaohsiung Medical University, Taiwan

National Cheng Kung University, Taiwan

Tainan Hospital, Taiwan

: J Spine Neurosurg

Abstract

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Objectives: Bipolar II disorder (BP-II), characterized by recurrent dysregulation of mood, is a serious and chronic psychiatric illness. However, BP-II is commonly under-recognized, even in psychiatric settings. Because dopaminergic disturbance is thought to be involved in the development of bipolar disorder (BPD), it seems essential to investigate dopamine-related genes like the catechol-O-methyltransferase (COMT) gene, which are involved in dopamine metabolism, and the methylenete trahydrofolate reductase (MTHFR) gene, which may affect COMT methylation and COMT function. The current study examined the association and interaction of the COMT Val158Met and MTHFR C677T variants with BP-II. Methods: Nine hundred seventy-eight participants were recruited: 531 with BP-II and 447 healthy controls. The genotypes of the COMT and MTHFR polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Results: After the MTHFR C677T genotypes in BP-II patients and Controls had been stratified, the COMT Val/Val variant was significantly more frequently detected in controls than in BP-II patients (P=0.008). Logistic regression analysis showed a significant interaction effect of the COMT Val158Met Val/Val genotype and the MTHFR C677T C/T+T/T genotype (OR=0.57, P=0.039) for the protective effect on the odds of developing BP-II. Conclusion: Our findings support preliminary evidence that the COMT and MTHFR genes interact in BP-II, and they imply the connection of both dopaminergic pathways and methylation pathways in the pathogenesis of BP-II.

Biography

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