한국인 조현병 환자에서의 지연성 운동이상증과 TNF (Tumor Necrosis Factor)-α 유전자 다형성과의 연관성
Association between Tardive Dyskinesia and Polymorphisms of TNF-α Gene in Korean Schizophrenia Patients
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초록
지연성 운동이상증은 항정신병 약물을 장기간 복용하는 조현병 환자에서 발생하는 비가역적인 부작용으로, 여러 새로운항정신병 약물이 개발된 현재에도 가장 심각한 부작용으로 여겨지고 있다. 따라서 조현병 환자 중 지연성 운동이상증의 발생에 감수성을 가지는 환자를 예측할 수 있다면 그 예방과 치료에 많은 도움이 될 것이다. 이러한 배경하에 본 연구는 한국인조현병 환자를 대상으로 TNF-α 유전자의 유전자 다형성과 지연성 운동이상증의 연관성을 알아보기 위해 시행되었으나, 지연성 운동이상증의 발생에 있어 TNF-α 유전자 다형성이 유전적 감수성의 원인이 됨을 밝히지는 못 하였다. 그러나 현재까지 지연성 운동이상증과 TNF-α 유전자 다형성 간의 연관성에 대한 연구가 극히 부족한 실정에서, 본 연구는 TNF-α 뿐 아니라 나아가 시토카인과 지연성 운동이상증의 발생에 대한 향후의 연구들에 있어 일말의 단서를 제공한다고 할 수 있겠다. 추후 보다 다양한 임상적 변인을 포함하여 TNF-α 유전자 다형성과 지연성 운동이상증의 관련성에 대한 연구가 이루어져야 할 것이다. 또한 지연성 운동이상증과 시토카인에 대한다른 후보유전자와의 연관 연구가 지연성 운동이상증의 병태생리학적 기전을 이해하는 데 도움을 줄 것으로 생각된다.
Abstract
Objectives : There are emerging evidences suggest that the development of tardive dyskinesia (TD) is related to the oxidative stress, excitotoxicity, and immune activation. The purpose of this study is to investigate whether single-nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF)-α genes are associated with the susceptibility of TD and schizophrenia. Methods : We investigated two hundred and eighty Korean schizophrenic patients. The schizophrenic participants consisted of patients with (n=105) and without (n=175) TD who were matched for antipsychotic drug exposure and other relevant variables. The TNF-α gene -308G/A SNPs were analyzed by polymerase chain reaction (PCR)-based methods. Results : The frequencies of genotype (χ2=0.33, p=0.848) of the TNF-α gene -308 G/A SNP did not differ significantly between schizophrenic patients with and without TD. The difference of allele frequencies (χ2=0.28, p=0.594) of the TNF-α gene between the schizophrenic patients with and without TD were not significant. Conclusion : These results suggest that the TNF-α gene -308 G/A SNPs are not associated with TD and schizophrenia in a Korean population. Further association studies of TD with other candidate genes for cytokines would help us understand the pathophysiological mechanisms of TD.
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