Noble E P, Syndulko K, Fitch R J, Ritchie T, Bohlman M C, Guth P, Sheridan P J, Montgomery A, Heinzmann C, Sparkes R S
Alcohol Research Center, Neuropsychiatric Institute, University of California, Los Angeles 90024.
Alcohol Alcohol. 1994 Nov;29(6):729-44.
The prevalence of TaqI A alleles of the D2 dopamine receptor (DRD2) gene was examined in two subgroups of medically ill nonalcoholics (more prevalent and less prevalent substance users, MPSU and LPSU, respectively) and in two subgroups of medically ill alcoholics (more severe and less severe alcoholics, MSA and LSA, respectively). The prevalence of the A1 allele in the 80 nonalcoholic and 73 alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009). In the four subgroups of these patients, the prevalence of this allele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA = 58.3%. Linear trend analysis showed that as the use of substances and severity of alcoholism increase, so does A1 prevalence (P = 0.001). Specific, subgroup comparisons showed A1 prevalence in MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04) higher than in LPSU and MPSU subgroups, respectively. Similarly, in a combined analysis of independent studies, A1 prevalence in MSA was higher when compared to LSA (P < 5 x 10(-3), MPSU (P < 10(-4) and LPSU (P < 10(-8) subgroups. There was virtually no difference in the prevalence of the A1 allele between LSA and MPSU subgroups. None of the specific medical or neuropsychiatric complications of alcoholism was associated with the A1 allele. In conclusion, the severity of alcohol dependence in alcoholics and of substance use behaviors in controls are important variables in DRD2 allelic association. The present report and converging lines of evidence suggest that the DRD2 locus could represent a prominent gene risk factor for susceptibility to severe alcoholism. However, other genes and environmental factors, when combined, still play the larger role.
在两组患有内科疾病的非酒精依赖者（分别为物质使用较频繁组和较不频繁组，即MPSU和LPSU）以及两组患有内科疾病的酒精依赖者（分别为酒精依赖较严重组和较不严重组，即MSA和LSA）中，研究了多巴胺D2受体（DRD2）基因的TaqI A等位基因的流行情况。80名非酒精依赖者和73名酒精依赖者中A1等位基因的流行率分别为30.0%和52.1%（P = 0.009）。在这些患者的四个亚组中，该等位基因的流行率分别为：LPSU = 18.2%，MPSU = 34.5%，LSA = 44.4%，MSA = 58.3%。线性趋势分析表明，随着物质使用和酒精依赖严重程度的增加，A1等位基因的流行率也增加（P = 0.001）。具体的亚组比较显示，MSA中A1等位基因的流行率分别比LPSU和MPSU亚组高约3倍（P = 0.007）和1.5倍（P = 0.04）。同样，在独立研究的综合分析中，与LSA（P < 5×10⁻³）、MPSU（P < 10⁻⁴）和LPSU（P < 10⁻⁸）亚组相比，MSA中A1等位基因的流行率更高。LSA和MPSU亚组之间A1等位基因的流行率几乎没有差异。酒精依赖的任何特定内科或神经精神并发症均与A1等位基因无关。总之，酒精依赖者中酒精依赖的严重程度以及对照组中物质使用行为是DRD2等位基因关联中的重要变量。本报告及一系列相互印证的证据表明，DRD2基因座可能是严重酒精依赖易感性的一个重要基因危险因素。然而，其他基因和环境因素综合起来仍发挥着更大的作用。
