Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pharmacogenet Genomics. 2010 Aug;20(8):500-6. doi: 10.1097/FPC.0b013e32833caa2b.
Clarifying the association between bipolar I and bipolar II, the two most common subtypes of bipolar disorder, at the genetic level is essential for improving our understanding of these disorders. The dopaminergic system has been implicated in the pathogenesis of bipolar disorder. It may be important to investigate genes involved in metabolizing dopamine and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) genes. We examined the association of the ALDH2 and DRD2/ANKK1 Taq IA polymorphisms with bipolar I and II disorders and possible interactions between these genes.
Seven hundred and fifty participants were recruited: 207 with bipolar I disorder, 277 with bipolar II disorder, and 266 healthy controls. The genotypes of the ALDH2 and DRD2/ANKK1 TaqIA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.
Logistic regression analysis showed a statistically significant interaction for the A1/A1 genotype of the DRD2/ANKK1 TaqIA, and the ALDH211 genotypes (P=0.009) could predict bipolar II patients compared with individuals without bipolar disorder. However, there was no association between the ALDH2 or DRD2/ANKK1 gene with neither bipolar I nor bipolar II disorder.
Our findings may provide initial evidence that the ALDH2 and DRD2/ANKK1 genes interact in specific subtypes of bipolar disorders. Our findings also suggest a unique genetic distinction between bipolar I and bipolar II disorders.
在遗传水平上阐明双相情感障碍两种最常见亚型（I 型和 II 型）之间的关联，对于加深我们对这些疾病的认识至关重要。多巴胺能系统与双相情感障碍的发病机制有关。研究参与多巴胺代谢和编码多巴胺受体的基因（如乙醛脱氢酶 2（ALDH2）和多巴胺 D2 受体/锚蛋白重复和激酶结构域包含 1（DRD2/ANKK1）基因）可能很重要。我们检查了 ALDH2 和 DRD2/ANKK1 TaqIA 多态性与双相 I 型和 II 型障碍的关联，以及这些基因之间可能的相互作用。
共招募了 750 名参与者：207 名双相 I 型障碍患者，277 名双相 II 型障碍患者和 266 名健康对照者。使用聚合酶链反应加限制性片段长度多态性分析确定 ALDH2 和 DRD2/ANKK1 TaqIA 多态性的基因型。
Logistic 回归分析显示，DRD2/ANKK1 TaqIA 的 A1/A1 基因型和 ALDH211 基因型之间存在统计学显著的相互作用（P=0.009），与无双相障碍者相比，A1/A1 基因型可预测双相 II 型患者。然而，ALDH2 或 DRD2/ANKK1 基因与双相 I 型或双相 II 型障碍均无关联。
我们的研究结果可能提供初步证据，表明 ALDH2 和 DRD2/ANKK1 基因在特定的双相情感障碍亚型中相互作用。我们的研究结果还表明，双相 I 型和双相 II 型障碍之间存在独特的遗传差异。
