양극성 장애에서 표피성장인자의 유전적 다형성에 대한 연합연구
Association between EGF A61G Polymorphism and Bipolar Disorder in Korean Population
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초록
EGF는 그 세포 내 작용 기전이나 신경세포에 미치는 영향, 유전 연구 결과 등을 종합할 때 양극성 장애의 발병과 관련될 가능성을 가지고 있다. 하지만 기존의 연합 연구가 정신분열병 환자들에 국한되어 있어 본 연구에서는 양극성 장애 환자들을 대상으로 연합연구를 시행하였다. 189명의 양극성 장애 환자군과 347명의 정상대조군을 비교한 결과 EGF와 양극성 장애 발병 사이의 연합은 관찰되지 않아 EGF가 양극성 장애의 발병과 직접적으로 관련될 가능성은 낮은 것으로 나타났다. 다만 양극성 장애 II형을 가진 여자 환자에서 AG 유전자형이 더 많이 관찰되었는데 본 연구에 참여한 양극성 장애 II형 환자의 표본수가 적은 것을 고려할 때 EGF가 이 유형의 질병 발현에 영향을 줄 가능성에 대해 향후 추가적인 연구가 필요하겠다.
Abstract
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. (J Korean Neuropsychiatr Assoc 2007;46(6):573-578)
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