Haberstick Brett C, Timberlake David, Smolen Andrew, Sakai Joseph T, Hopfer Christian J, Corley Robin P, Young Susan E, Stallings Michael C, Huizinga David, Menard Scott, Hartman Christy, Grotpeter Jennifer, Hewitt John K
Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO 80309-0447, USA.
J Stud Alcohol Drugs. 2007 May;68(3):362-70. doi: 10.15288/jsad.2007.68.362.
Dopaminergic dysfunction has been hypothesized to play an important role in the etiology of alcohol-use disorders. A restriction fragment length polymorphism (RFLP) in the 3' untranslated region (3'UTR) of the DRD2 gene affects gene expression and has been implicated as a risk factor for alcohol dependence. This polymorphism (TaqIA) has been reported as positively associated with alcohol-use disorders in case-control samples, but these results have not been replicated in family-based association studies. The mixed results of association between the DRD2 TaqIA polymorphism and alcohol-use disorders may be the result of differences in sample size, phenotype definition, heterogeneity of the samples, and genetic admixture.
We conducted tests of association in a sample of 838 adults participating in the National Youth Survey Family Study (NYSFS). We examined whether the DRD2 TaqIA polymorphism was associated with a symptom-count measure of alcohol abuse and dependence derived from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Craving Withdrawal Model.
Tests of association were nonsignificant across each classification system examined. Power calculations suggested that these results were despite the ability to detect an effect size of 1%.
This study supports other family-based association tests that have reported no association between the DRD2 TaqIA polymorphism and alcohol abuse and dependence.
多巴胺能功能障碍被认为在酒精使用障碍的病因学中起重要作用。DRD2基因3'非翻译区(3'UTR)的限制性片段长度多态性(RFLP)影响基因表达,并被认为是酒精依赖的一个危险因素。这种多态性(TaqIA)在病例对照样本中已被报道与酒精使用障碍呈正相关,但这些结果在基于家系的关联研究中尚未得到重复验证。DRD2 TaqIA多态性与酒精使用障碍之间关联结果的不一致,可能是由于样本量、表型定义、样本异质性以及基因混合等方面的差异所致。
我们在838名参与全国青年调查家庭研究(NYSFS)的成年人样本中进行了关联测试。我们检验了DRD2 TaqIA多态性是否与源自《精神障碍诊断与统计手册》第四版及渴望戒断模型的酒精滥用和依赖症状计数指标相关。
在所检验的每个分类系统中,关联测试均无显著性。功效计算表明,尽管有能力检测到1%的效应量,但仍得出了这些结果。
本研究支持其他基于家系的关联测试结果,即DRD2 TaqIA多态性与酒精滥用及依赖之间无关联。