The ALDH2 and 5-HT2A genes interacted in bipolar-I but not bipolar-II disorder

Objective: Clarifying the similarities and differences between the two most common subtypes of bipolar disorder, bipolar-I and bipolar-II, is essential for improving our understanding of them. Because the serotonergic system has been implicated in the pathogenesis of bipolar disorder, it may be important to investigate genes such as the aldehyde dehydrogenase 2 (ALDH2) and serotonin 2A receptor genes, which are involved in metabolizing serotonin and encoding serotonin receptors. We examined the association of the ALDH2 and 5-HT2A-A1438G polymorphisms with bipolar I and II and possible interactions between these genes.

Methods: One thousand forty-nine participants were recruited: 249 with bipolar-I, 456 with bipolar-II, and 344 healthy controls. The genotypes of the ALDH2 and 5HT2A-A1438G polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results: Logistic regression analysis showed a significant effect of the ALDH2 and the 5-HT2A-A1438G polymorphisms, and a significant interaction effect for the A/G genotypes of the 5-HT2A-A1438G polymorphism and the ALDH2*1*1 genotypes (p=0.004) discriminated between bipolar-I patients and controls without bipolar disorder. These polymorphisms, however, were not associated with bipolar-II disorder.

Limitations: The significant differences of age and gender between patients and controls limit the comparison, although statistical adjustments were made for them.

Conclusion: Our findings provide initial evidence that the ALDH2 and 5-HT2A genes interact in bipolar-I but not in bipolar-II disorder. Our findings suggest a unique genetic distinction between bipolar-I and bipolar-II.