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韩国酗酒者子女中多巴胺D2、D4受体基因、GABAA受体β亚基基因、5-羟色胺转运体基因多态性的关联研究:一项初步研究。

Association study of dopamine D2, D4 receptor gene, GABAA receptor beta subunit gene, serotonin transporter gene polymorphism with children of alcoholics in Korea: a preliminary study.

作者信息

Namkoong Kee, Cheon Keun-Ah, Kim Jae-Won, Jun Jin-Yong, Lee Jun-Young

机构信息

Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Alcohol. 2008 Mar;42(2):77-81. doi: 10.1016/j.alcohol.2008.01.004.

Abstract

The studies on the genetic risk factors of the children of alcoholics (COAs) are still in an early stage. The A1 allele of the dopamine receptor 2 gene (DRD2) may be associated with positive alcohol expectancy of the COAs. In addition, several researchers reported that the COAs might be associated with the GABA A receptor beta3 subunit gene (GABRB3) and serotonin transporter gene (5-HTTLPR). In this study, we investigated the association of the polymorphism of the DRD2, Dopamine D4 receptor gene (DRD4), GABRB3, 5-HTTLPR with the COAs. Twenty-two COAs and 23 age and sex-matched control children were included for the genetic study (children of nonAlcoholics; nonCOAs). All COAs aged 6-18 were recruited and selected from family of alcoholic patients in Alcohol Clinic of the University hospital. The genotyping of the DRD2, DRD4, GABRB3, 5-HTTLPR was carried out. We used the Chi-square method for evaluating the association of genetic polymorphic allelic status with the COAs. The frequency of the A1+ allele at DRD2 in the COAs was significantly higher than nonCOAs. Significant association between the genotype at DRD4 and the COAs was found. The G1- alleles of the GABRB3 in COAs were significantly higher than nonCOAs. However, no association of the polymorphic alleles of the 5-HTTLPR with the COAs was found. We found that the children of alcoholics had a significantly increased number of risk alleles of candidate genes of alcohol drinking expectancy. Despite of several limitations, 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.

摘要

对酗酒者子女(COAs)遗传风险因素的研究仍处于早期阶段。多巴胺受体2基因(DRD2)的A1等位基因可能与COAs对酒精的积极预期有关。此外,一些研究人员报告称,COAs可能与γ-氨基丁酸A受体β3亚基基因(GABRB3)和血清素转运体基因(5-HTTLPR)有关。在本研究中,我们调查了DRD2、多巴胺D4受体基因(DRD4)、GABRB3、5-HTTLPR的多态性与COAs之间的关联。基因研究纳入了22名COAs以及23名年龄和性别匹配的对照儿童(非酗酒者的子女;非COAs)。所有6至18岁的COAs均从大学医院酒精诊所的酒精依赖患者家庭中招募和选取。对DRD2、DRD4、GABRB3、5-HTTLPR进行基因分型。我们使用卡方检验方法评估基因多态性等位基因状态与COAs之间的关联。COAs中DRD2基因A1 +等位基因的频率显著高于非COAs。发现DRD4基因的基因型与COAs之间存在显著关联。COAs中GABRB3基因的G1 -等位基因显著高于非COAs。然而,未发现5-HTTLPR基因多态性等位基因与COAs之间存在关联。我们发现,酗酒者的子女中,与饮酒预期相关的候选基因的风险等位基因数量显著增加。尽管存在一些局限性,但本研究提供了一些关于与COAs相关的风险和保护因素的初步信息,可作为未来精神病理学预防和干预的基础。

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