The ALDH2 and DRD2/ANKK1 genes interacted in bipolar II but not bipolar I disorder.
OBJECTIVE
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.


METHODS
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.


RESULTS
Logistic regression analysis showed a statistically significant interaction for the A1/A1 genotype of the DRD2/ANKK1 TaqIA, and the ALDH2*1*1 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.


CONCLUSIONS
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.
Lee
Sheng-Yu
SY
Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chen
Shiou-Lan
SL
Chang
Yun-Hsuan
YH
Chen
Shih-Heng
SH
Chu
Chun-Hsieh
CH
Huang
San-Yuan
SY
Tzeng
Nian-Sheng
NS
Wang
Chen-Lin
CL
Lee
I Hui
IH
Yeh
Tzung Lieh
TL
Yang
Yen Kuang
YK
Lu
Ru-Band
RB
D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001714:Bipolar Disorder / Q000145:classification* / Q000201:enzymology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D017448:Receptors, Dopamine D2; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases