Blum K, Noble E P, Sheridan P J, Finley O, Montgomery A, Ritchie T, Ozkaragoz T, Fitch R J, Sadlack F, Sheffield D
Laboratory of Pharmacogenetics, University of Texas Health Science Center, San Antonio 78284.
Alcohol. 1991 Sep-Oct;8(5):409-16. doi: 10.1016/0741-8329(91)90693-q.
In a blinded study, 159 subjects composed of nonalcoholics (N = 43), less severe alcoholics (N = 44), severe alcoholics (N = 52) and young children of alcoholics (CoAs, N = 20) were studied for their allelic association with the D2 dopamine receptor (D2DR) gene utilizing peripheral lymphocytes as the DNA source. The combined alcoholic group compared to the nonalcoholic group showed a significantly greater association with the A1 allele of the D2DR gene. Furthermore, an even more robust association was found when severe alcoholics were compared to nonalcoholics. CoAs also showed a significantly greater association with the A1 allele than nonalcoholics but not when compared to alcoholics. Analysis of risk of alcoholism severity suggests that it comprises of two independent components: family history of alcoholism and presence of the A1 allele. Genotype and allelic frequency of the D2DR gene were also analyzed with respect to race. A higher percentage of blacks compared to whites had the A1/A1 genotype, and A1 allelic frequency in the total sample of blacks was significantly greater than in the total sample of whites. Moreover, frequency of the A1 allele was significantly greater in severe alcoholics compared to nonalcoholics in both whites and blacks. However, due to the small sample size of blacks, these racial differences need to be further studied. This study, of the largest sample of alcoholics to date, strongly affirms association of severe alcoholism with the A1 allele of the D2DR gene.
在一项双盲研究中，以外周淋巴细胞作为DNA来源，对由非酗酒者（N = 43）、轻度酗酒者（N = 44）、重度酗酒者（N = 52）和酗酒者的幼儿（N = 20）组成的159名受试者进行了D2多巴胺受体（D2DR）基因的等位基因关联研究。与非酗酒组相比，酗酒者合并组与D2DR基因的A1等位基因的关联显著更强。此外，将重度酗酒者与非酗酒者进行比较时，发现关联更强。酗酒者的幼儿与A1等位基因的关联也显著强于非酗酒者，但与酗酒者相比则不然。对酗酒严重程度风险的分析表明，它由两个独立的因素组成：酗酒家族史和A1等位基因的存在。还针对种族分析了D2DR基因的基因型和等位基因频率。与白人相比，黑人中具有A1/A1基因型的比例更高，黑人总样本中的A1等位基因频率显著高于白人总样本。此外，在白人和黑人中，重度酗酒者的A1等位基因频率均显著高于非酗酒者。然而，由于黑人样本量较小，这些种族差异需要进一步研究。这项对迄今为止最大样本的酗酒者进行的研究，有力地证实了重度酗酒与D2DR基因的A1等位基因之间的关联。
