한국인 알코올 의존 자녀들과 도파민 D2, D4 수용체, GABAA 수용체 β Subunit 및 세로토닌 운반체 유전자 다형성 사이의 연관성에 대한 예비적 연구

Association Study of Dopamine D2, D4 Receptor Gene, GABAA Receptor βSubunit Gene, and Serotonin Transporter Gene Polymorphism with Children of Alcoholics in Korea : Preliminary Study

Objectives：The studies on the genetic risk factors of the children of alcoholics (COAs) are still in an early stage. The A 1 allele of the dopamine receptor 2 gene (DRD2) may be associated with the negative affect and positive alcohol expectancy of the COAs. In addition, several researchers reported that COAs might be associated with the GABAA receptor β subunit gene (GABRB3) and serotonin transporter gene (5-HTTLPR). In this study, we investigated the association of polymorphism of the DRD2, Dopamine D4 receptor gene (DRD4), GABRB3, 5-HTTLPR with COAs to examine the genetic risk factors of COAs. Methods：Twenty-two COAs and 23 control children (children of non-Alcoholics；Non-COAs) were included for the genetic study. All COAs aged 6 to 18 were recruited and selected from families of alcoholic patients in alcohol clinics of three university and mental hospital. Alcoholism of parents was classified as type I (non-antisocial, late onset) and type II (antisocial, early onset) by Cloninger’s classification. The genotyping of the DRD2, DRD4, GABRB3, 5-HTTLPR was carried out. Chi-square method was used for evaluating the associations between genetic polymorphism and the COAs. Results：The frequency of A1+ allele of DRD2 in COAs were significantly higher than Non-COAs (χ2=4.45, df=1, p= 0.035). Significant association between the genotype of DRD4 and COAs was found (χ2=8.32, df=1, p=0.004). G1- alleles of GABRB3 in COAs were significantly higher than in Non-COAs (χ2=6.622, df=1, p=0.022). We found no association of the polymorphic alleles of 5-HTTLPR with the COAs (χ2=0.021, df=1, p=0.884). There were significant associations between the type of parental alcoholism and depression of COAs. Conclusion：We found that the children of alcoholics had significantly increased genetic risk of alcohol drinking expectancy. This study provides some preliminary information on the risk and protective factors associated with the COAs, which can be used as a foundation for prevention and intervention of future psychopathology.