Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
World J Biol Psychiatry. 2011 Aug;12(5):385-91. doi: 10.3109/15622975.2010.505298. Epub 2010 Aug 10.
OBJECTIVES. Clarifying the association between bipolar I and bipolar II disorders at the genetic level is essential for improving our understanding of them. In this study, we evaluated the hypothesis that the dopaminergic polymorphisms are risk factors for bipolar disorders. We examined the association between the catechol-O-methyltransferase (COMT) Val158Met and dopamine D3 receptor (DRD3) Ser9Gly polymorphisms and bipolar I and II disorders, as well as possible interactions between these genes. METHODS. Seven hundred and eleven participants were recruited: 205 with bipolar I, 270 with bipolar II, and 236 healthy controls. The genotypes of the COMT Val158Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS. Logistic regression analyses showed a statistically significant main effect for the Met/Met genotype of the COMT Val158Met polymorphism (P=0.032) and a significant interaction effect for the Met/Met genotype of the COMT Val158Met and Ser/Ser genotypes of the DRD3 Ser9Gly polymorphism (P=0.001) predicted bipolar I patients. However, there was no association between the COMT Val158Met or DRD3 Ser9Gly and bipolar II. CONCLUSIONS. We provide initial evidence that the COMT Val158Met and DRD3 Ser9Gly genotypes interact in bipolar I and bipolar II disorders and that bipolar I and bipolar II are genetically distinct.
从遗传学角度阐明双相 I 型和双相 II 型障碍之间的关联对于加深我们对其的认识至关重要。本研究旨在评估多巴胺能多态性是否为双相障碍的风险因素这一假说。我们检验了儿茶酚-O-甲基转移酶（COMT）Val158Met 和多巴胺 D3 受体（DRD3）Ser9Gly 多态性与双相 I 型和 II 型障碍之间的关联，以及这些基因之间可能存在的相互作用。方法：共纳入 711 名参与者，其中 205 名患有双相 I 型障碍，270 名患有双相 II 型障碍，236 名健康对照。采用聚合酶链反应加限制性片段长度多态性分析方法确定 COMT Val158Met 和 DRD3 Ser9Gly 多态性的基因型。结果：Logistic 回归分析显示，COMT Val158Met 多态性的 Met/Met 基因型具有统计学显著的主效应（P=0.032），而 COMT Val158Met 多态性的 Met/Met 基因型和 DRD3 Ser9Gly 多态性的 Ser/Ser 基因型之间存在显著的相互作用效应（P=0.001），可预测双相 I 型患者。然而，COMT Val158Met 或 DRD3 Ser9Gly 多态性与双相 II 型之间均无关联。结论：本研究初步证实，COMT Val158Met 和 DRD3 Ser9Gly 基因型在双相 I 型和双相 II 型障碍中相互作用，且双相 I 型和双相 II 型在遗传学上存在差异。
