조현병 환자와 건강한 대조군의 인지기능에서 COMT와 DTNBP1의 상호작용과의 관련성

Abstract

목적: 아직까지 조현병의 원인은 뚜렷하게 밝혀지지 않았지만, 유전 연구를 통해 COMT와 DTNBP1을 포함한 여러 유전자가 조현병의 발병 및 인지기능과 관련이 있는 것으로 보고하고 있다. 하지만 특정 유전자가 발현 형질로 나타날 때, 다른 유전자가 영향을 주는 현상인 상위성(epistasis)에 대한 연구는 거의 이루어지지 않았다. 이에 본 연구는 대조군과 조현병 환자군의 인지기능에서 COMT와 DTNBP1 유전자의 영향을 확인하고자 한다.

방법: DSM-IV의 조현병 진단 기준에 부합하는 환자군(N=122)과 대조군(N=119)을 대상으로 신경심리검사를 시행하였고, 그 결과를 The Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS) Consensus Cognitive Battery를 통해 6가지 인지 영역인 처리속도, 작업 기억, 언어적 학습과 기억, 시각적 학습과 기억, 주의집중/각성, 추론과 문제 해결로 소급하고, COMT rs4680과 DTNBP1 rs1011313, rs760761, rs2619539, rs3213207, rs1018381, SNPnew간의 상호작용을 평가하였다.

결과 : 대조군과 비교하여 환자군이 신경심리검사의 모든 인지 영역에서 낮은 수행을 보였다. 나이, 성별, 교육 수준을 보정 한 후, COMT와 DTNBP1의 상호작용의 상관관계를 조사한 결과, 환자군에서 DTNBP1 rs760761이 시각적 학습과 기억 영역의 부가모형에서 COMT rs4680과의 상호작용이 유의미한 상관 관계를 보였으며 (p=0.041), COMT rs4680과 DTNBP1 rs1018381와의 상호작용은 시각적 학습과 기억 영역의 부가모형 (p=0.011), 우성모형 (p=0.024)에서 유의미한 상관관계를 보였다.

결론: COMT rs4680과 DTNBP1 rs760761, rs1018381간의 상호작용이 조현병 환자의 인지기능에 영향을 미칠 수 있다.|Objective: The cause of schizophrenia has yet to be clarified, but genetic studies suggest that several genes, including Catechol-O-methyl transferase (COMT) and Dystrobrevin binding protein1 (DTNBP1), are associated with the development and cognitive function of schizophrenia. However, little research has been done on epistasis, a phenomenon in which other genes affect when a particular gene appears as an expression trait. The aim of this study was to determine the effects of COMT and DTNBP1 genes on cognitive function in control and schizophrenic patients.

Method: Neuropsychological tests were performed in patients (N = 122) and controls (N = 119) who met the schizophrenia diagnosis criteria of DSM-IV. The results were measured by The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus cognitive Battery retroactively as six cognitive domains, processing speed, working memory, verbal learning and memory, visual learning and memory, attention / vigilance, and reasoning and problem solving. The interaction between COMT rs4680 and DTNBP1 rs1011313, rs760761, rs2619539, rs3213207, rs1018381 and SNPnew was evaluated.

Result : Compared to the control group, the patient group showed low performance in all cognitive domains of the neuropsychological test. After calibrating age, sex, and education, the correlation between COMT and DTNBP1 was investigated. DTNBP1 rs760761 showed significant correlation between COMT rs4680 and the visual learning and memory domain in the patient group. (P = 0.041) and the interaction between COMT rs4680 and DTNBP1 rs1018381 showed significant correlation between visual learning and memory domain addition model (p = 0.011) and dominant model (p = 0.024).

Conclusion: The interaction between COMT rs4680, DTNBP1 rs760761, and rs1018381 may affect the cognitive function of schizophrenia patients.; Objective: The cause of schizophrenia has yet to be clarified, but genetic studies suggest that several genes, including Catechol-O-methyl transferase (COMT) and Dystrobrevin binding protein1 (DTNBP1), are associated with the development and cognitive function of schizophrenia. However, little research has been done on epistasis, a phenomenon in which other genes affect when a particular gene appears as an expression trait. The aim of this study was to determine the effects of COMT and DTNBP1 genes on cognitive function in control and schizophrenic patients.

Method: Neuropsychological tests were performed in patients (N = 122) and controls (N = 119) who met the schizophrenia diagnosis criteria of DSM-IV. The results were measured by The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus cognitive Battery retroactively as six cognitive domains, processing speed, working memory, verbal learning and memory, visual learning and memory, attention / vigilance, and reasoning and problem solving. The interaction between COMT rs4680 and DTNBP1 rs1011313, rs760761, rs2619539, rs3213207, rs1018381 and SNPnew was evaluated.

Result : Compared to the control group, the patient group showed low performance in all cognitive domains of the neuropsychological test. After calibrating age, sex, and education, the correlation between COMT and DTNBP1 was investigated. DTNBP1 rs760761 showed significant correlation between COMT rs4680 and the visual learning and memory domain in the patient group. (P = 0.041) and the interaction between COMT rs4680 and DTNBP1 rs1018381 showed significant correlation between visual learning and memory domain addition model (p = 0.011) and dominant model (p = 0.024).

Conclusion: The interaction between COMT rs4680, DTNBP1 rs760761, and rs1018381 may affect the cognitive function of schizophrenia patients.