양극성 장애에서 표피성장인자의 유전적 다형성에 대한 연합연구

Association between EGF A61G Polymorphism and Bipolar Disorder in Korean Population

Objectives：Epidermal growth factor (EGF) is a neurotrophic factor which regulates the intracellular signaling molecules. These molecules are also affected by mood stabilizers such as lithium and valproate. In addition, epidermal growth factor enhances neuronal survival, maturation and differentiation especially in midbrain dopaminergic neurons of which dysfunction may play a role in pathophysiology of bipolar disorders. Bipolar disorder has some genetic commonalities with schizophrenia, and several association studies of EGF have been done with schizophrenia. In this study, we tried to investigate the genetic association between EGF A61G polymorphism and bipolar disorder. Methods：Total of 189 patients and 347 normal control were included. All patients satisfied the diagnostic criteria of DSMIV for bipolar disorder type I (BPDI, N=146) and bipolar disorder type II (BPDII, N=43). Genomic DNA was extracted from the peripheral blood, and genotyping was performed by TaqManTM method. Genotype and allele frequency of EGF A61G polymorphism between the patients and the control were compared by contingency chi-square test or the Fisher’s exact test. Results：No association was found between EGF A61G polymorphism and susceptibility of BPDI, BPDII and bipolar disorder (all patients). Female patients with BPDII showed overexpression of AG genotype compared to that of control group (p=0.03). However, this association was not significant after correction of multiple testing. Conclusion：In conclusion, EGF A61G polymorphism has no association with susceptibility of bipolar disorder. However, the disease modifying role of EGF gene polymorphism for bipolar disorder remains to be elucidated in respect to factors such as gender difference or diagnostic subtype.