Matsushita Sachio, Kimura Mitsuru, Miyakawa Tomohiro, Yoshino Aihide, Murayama Masanobu, Masaki Toshihiro, Higuchi Susumu
National Hospital Organization, Kurihama Alcoholism Center, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan.
Alcohol Clin Exp Res. 2004 Nov;28(11):1609-12. doi: 10.1097/01.alc.0000145697.81741.d2.
Brain-derived neurotrophic factor (BDNF) influences dopamine and serotonin neurotransmitters that are heavily linked to addiction. A quantitative trait loci study indicated that genes localized to 11p13, where the BDNF gene is mapped (11p13-15), increase the risk for severe alcohol withdrawal. Moreover, a recent study using a pooled-sample microarray suggested that the BDNF gene locus was included in the loci that were shown to be associated with drug abuse. These lines of evidence suggested that BDNF might play some role in the development of or vulnerability to alcoholism and/or clinical characteristics of alcoholic individuals.
The alcoholic subjects consisted of 377 male Japanese patients. A structured interview was used to obtain social background, drinking history, history of violence while intoxicated, history of alcohol withdrawal, and family history of alcoholism. The control group consisted of 336 nonalcoholic male subjects. Genotyping of the G196A polymorphism of the BDNF gene was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism method.
Genotype and allele distributions of the BDNF gene polymorphism did not differ significantly between alcoholic and control subjects. However, comparing clinical characteristics across G196A genotypes, we found that alcoholic subjects with violent tendencies and a history of delirium tremens had a significantly higher frequency of AA genotypes and A allele frequencies than those without them. Moreover, alcoholic subjects with the A allele had earlier onset of the disease than those without it.
These results indicate that BDNF gene polymorphism might modify phenotypes of alcoholism.
脑源性神经营养因子（BDNF）会影响与成瘾密切相关的多巴胺和5-羟色胺神经递质。一项数量性状基因座研究表明，定位在11p13（BDNF基因所在位置，11p13 - 15）的基因会增加严重酒精戒断的风险。此外，最近一项使用混合样本微阵列的研究表明，BDNF基因座包含在显示与药物滥用相关的基因座中。这些证据表明，BDNF可能在酒精中毒的发生、易感性和/或酒精中毒个体的临床特征中发挥一定作用。
酒精中毒受试者包括377名日本男性患者。采用结构化访谈获取社会背景、饮酒史、醉酒时的暴力史、酒精戒断史和酒精中毒家族史。对照组由336名非酒精中毒男性受试者组成。采用聚合酶链反应（PCR）-限制性片段长度多态性方法对BDNF基因的G196A多态性进行基因分型。
BDNF基因多态性的基因型和等位基因分布在酒精中毒受试者和对照组之间无显著差异。然而，比较不同G196A基因型的临床特征时，我们发现有暴力倾向和震颤谵妄史的酒精中毒受试者的AA基因型和A等位基因频率显著高于无这些情况的受试者。此外，携带A等位基因的酒精中毒受试者发病年龄早于不携带该等位基因的受试者。
这些结果表明，BDNF基因多态性可能会改变酒精中毒的表型。
