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ADH1B와 NQO2 유전다 다형성이 알코올 의존의 발병연령과 금단증상에 미치는 영향

The Effect of ADH1B and NQO2 Polymorphisms on the Age of Onset of Alcohol Dependence and Alcohol Withdrawal Symptoms

조근호|서정석|한덕현|최삼욱|윤성구|이영식
대한신경정신의학회 (Korean Neuropsychiatric Association)|2007.05|신경정신의학 (JOURNAL OF THE KOREAN NEUROPSYCHIATRIC ASSOCIATION)|제46권 제3호|pp. 237-244

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알코올 의존·금단증상·ADH1B·NQO2·유전자다형성.Alcohol dependence· Alcohol withdrawal· ADH1B· NQO2· Polymorphism.
주제분류정신과학

초록

연구목적 : 알코올 분해효소인 ADH1B와 제2상 해독(phase II detoxification) 효소인 NQO2 유전자 다형성이 알코올 의존 발병과, 금단증상 형성에 어떤 영향을 미치는 지를 알아보기 위해 본 연구를 시행하였다. 방법 : 알코올 의존 남자 환자 194 명과 정상 대조군 152명을 대상으로 하였다. 알코올 의존은 25세를 기준으로 조기 발병군 68명과 후기 발병군 126명으로 나누어 비교하였다. ADH1B 및 NQO2의 유전자 분석은 중합효소반응(polymerase chain reaction: PCR)과 제한효소절편길이다형성(restriction fragment length polymorphism; RFLP)을 사용하였다. 금단증상의 측정은 임상 알코올 금단 척도(Clinical Institute Withdrawal Assessment for Alcohol Scale(CIWA-Ar)를 사용하였다. 결과: Alcohol dehydrogenase 1B(ADH1B) 유전형 분포는 환자군과 정상군간에 차이가 없었으나 후기 발병군에서 조기 발병군보다 ADH1B*2 (A) 대립유전자의 빈도가 높았다(p=0.015). NRH-quinone oxidoreductase 2 (NQO2) D 형 대립유전자 보유빈도는 환자군에서 정상인보다 높았으며(p=0.01), 후기 발병군에서 조기 발병군보다 높았다(p=0.01). CIWA-Ar scale 총점을 통해 본 금단증상은 ADH1B 유전자 다형성에 따른 차이가 없었으나, 환촉, 환시 소 항목에서 A 보유자의 점수가 높았다. NQO2의 경우 D 대립유전자 보유군에서 I/I형 보다 의미있게 높았다(p=0.04). 후기 발병군 중 ADH1B*2 (A) 대립유전자와 NQO2 D 대립유전자를 동시에 가지고 있는 환자의 odd ratio는 2.23 (p=0.02)이었다. 결론: ADH1B*2 대립 유전자와 NQO2 D 대립유전자는 금단증상의 발생과 관련이 있으며, 알코올 의존 발생의 지연 역할을 하는 가능성이 추정되었다.

Abstract

Objectives : We hypothesized that the polymorphisms of ADH1B and NQO2 could effect on the onset of alcohol dependence and withdrawal symptoms. Methods : PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism) were used to analyze the genetic polymorphisms of ADH1B and NQO2 in 194 male patients with alcohol dependence (AD) and 152 healthy comparisons. The AD were classified into the early and late onset groups with the onset age of 25. Alcohol withdrawal symptoms were measured by Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). Results : 1) Alcohol dehydrogenase 1B gene : There was no difference in genotype distribution between the patients group and the control group. However the frequency of ADH1B*2 allele in late-onset alcohol dependence was higher group than early-onset group. 2) NRH-quinone oxidoreductase 2(NQO2) : The patients group had higher frequency of D allele than the healthy comparisons. In patients group, the frequency of the D allele in the late-onset group was higher than he early-onset group. 3) CIWA-Ar scale : There was no difference in the CIWA-Ar scale between the genetic polymorphisms of ADH1B. However, the patients with D allele of NQO2 showed significantly higher scores in the CIWA-Ar scale than those with I/I allele. Conclusion : With current results, we suggested that ADH1B*2 and D allele of NQO2 would have a possible association with the alcohol withdrawal symptoms and play a protective role in the onset of alcohol dependence.

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