INSERM U675, IFR02, Université Paris 7, 16 Rue Henri Huchard, 75018 Paris, France.
Curr Genomics. 2008 Nov;9(7):444-51. doi: 10.2174/138920208786241252.
Alcohol dependence is a worldwide public health problem, and involves both environmental and genetic vulnerability factors. The heritability of alcohol dependence is rather high, ranging between 50% and 60%, although alcohol dependence is a polygenic, complex disorder.Genome-wide scans on large cohorts of multiplex families, including the collaborative study on genetics of alcoholism (COGA), emphasized the role of many chromosome regions and some candidate genes. The genes encoding the alcohol-metabolizing enzymes, or those involved in brain reward pathways, have been involved. Since dopamine is the main neurotransmitter in the reward circuit, genes involved in the dopaminergic pathway represent candidates of interest. Furthermore, gamma-amino-butyric acid (GABA) neurotransmitter mediates the acute actions of alcohol and is involved in withdrawal symptomatology. Numerous studies showed an association between variants within GABA receptors genes and the risk of alcohol dependence.In accordance with the complexity of the "alcohol dependence" phenotype, another field of research, related to the concept of endophenotypes, received more recent attention. The role of vulnerability genes in alcohol dependence is therefore re-assessed focusing on different phenotypes and endophenotypes. The latter include brain oscillations, EEG alpha and beta variants and alpha power, and amplitude of P300 amplitude elicited from a visual oddball task.Recent enhancement on global characterizations of the genome by high-throughput approach for genotyping of polymorphisms and studies of transcriptomics and proteomics in alcohol dependence is also reviewed.
酒精依赖是一个全球性的公共健康问题，涉及环境和遗传易感性因素。尽管酒精依赖是一种多基因、复杂的疾病，但它的遗传性相当高，范围在 50%到 60%之间。对包括酒精中毒遗传学合作研究（COGA）在内的多倍体家族的大型队列进行的全基因组扫描强调了许多染色体区域和一些候选基因的作用。编码酒精代谢酶的基因，或那些参与大脑奖励途径的基因，都参与其中。由于多巴胺是奖励回路中的主要神经递质，因此涉及多巴胺能途径的基因是感兴趣的候选基因。此外，γ-氨基丁酸（GABA）神经递质介导酒精的急性作用，并参与戒断症状。许多研究表明，GABA 受体基因内的变异与酒精依赖的风险之间存在关联。
根据“酒精依赖”表型的复杂性，另一个与内表型概念相关的研究领域最近受到了更多关注。因此，重新评估了易损基因在酒精依赖中的作用，重点关注不同的表型和内表型。后者包括脑振荡、EEG 阿尔法和贝塔变体以及阿尔法功率，以及从视觉Oddball 任务中诱发的 P300 振幅的幅度。最近还回顾了通过高通量方法对基因组进行全面特征描述的进展，包括多态性的基因分型研究以及转录组学和蛋白质组学在酒精依赖中的研究。
