Lee J F, Lu R B, Ko H C, Chang F M, Yin S J, Pakstis A J, Kidd K K
Graduate Institute of Medical Sciences, National Defense Medical Center, Armed Forces Pei-Tou Hospital, Taipei, Taiwan, Republic of China.
Alcohol Clin Exp Res. 1999 Apr;23(4):592-9.
Recent studies on the genetics of alcoholism have examined the association between alcoholism and the dopamine D2 receptor locus (DRD2); our study of Chinese Han gave negative results (Lu et al., 1996). The different genotypes at the genes encoding the enzymes involved in alcohol metabolism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males (Thomasson et al., 1991; Chen WJ et al., 1996; Chen CC et al., unpublished data). Therefore, association studies of alcoholism in Chinese Han might be more sensitive if controlled for the genotypes of ADH2,ADH3, and ALDH2, when other loci, such as DRD2, are examined. This study employs such controls to evaluate the evidence for an association between alcoholism and TaqI-A and TaqI-B genotypes and haplotypes at DRD2 in the Chinese Han population.
We studied 213 Chinese Han subjects (128 alcoholics and 85 nonalcoholics) with alcohol dependence defined according to DSM-III-R criteria.
Significant linkage disequilibrium was observed between the TaqI-A and TaqI-B sites at the DRD2 locus, as previously seen in smaller samples, but no significant association was observed between these genetic variants at the DRD2 locus and alcoholism in Chinese Han. Several different stratifications by ADH and ALDH2 genotypes were examined; no genotypes or haplotypes at DRD2 differ between alcoholics and nonalcoholics except for a small number of nominally significant p-values which do not constitute significant results given the many tests done, some of which are not independent of one another due to linkage disequilibrium. These tests included considering the high risk (ADH2*1/*1; *1/2; ADH31/*2; *2/2; and ALDH21/1) and the low risk (ADH22/2; ADH31/1; and ALDH21/*2; *2/*2) groups of alcoholics, as well as nonalcoholic controls.
After stratification by the relevant genotypes of ADH2, ADH3, and ALDH2 no significant association exists between the genetic variants at the DRD2 locus and alcoholism in the Chinese Han population.
近期关于酒精中毒遗传学的研究探讨了酒精中毒与多巴胺D2受体基因座（DRD2）之间的关联；我们对中国汉族人群的研究结果为阴性（Lu等人，1996年）。先前的研究表明，编码参与酒精代谢的酶的基因，即一类酒精脱氢酶（ADH2和ADH3）和线粒体乙醛脱氢酶（ALDH2）的不同基因型，在中国汉族男性中对酒精中毒的易感性不同（Thomasson等人，1991年；Chen WJ等人，1996年；Chen CC等人，未发表数据）。因此，在中国汉族人群中进行酒精中毒的关联研究时，如果在检测其他基因座（如DRD2）时控制ADH2、ADH3和ALDH2的基因型，可能会更敏感。本研究采用这种对照来评估中国汉族人群中酒精中毒与DRD2基因座上的TaqI-A和TaqI-B基因型及单倍型之间关联的证据。
我们研究了213名中国汉族受试者（128名酒精中毒者和85名非酒精中毒者），酒精依赖根据DSM-III-R标准定义。
在DRD2基因座的TaqI-A和TaqI-B位点之间观察到显著的连锁不平衡，如先前在较小样本中所见，但在中国汉族人群中，DRD2基因座的这些遗传变异与酒精中毒之间未观察到显著关联。对ADH和ALDH2基因型进行了几种不同的分层分析；除了少数名义上显著的p值外，酒精中毒者和非酒精中毒者在DRD2基因座上的基因型或单倍型没有差异，鉴于进行了大量检验，其中一些由于连锁不平衡并非相互独立，这些p值并不构成显著结果。这些检验包括考虑酒精中毒者的高风险组（ADH2*1/*1；*1/2；ADH31/*2；*2/2；以及ALDH21/1）和低风险组（ADH22/2；ADH31/1；以及ALDH21/*2；*2/*2）以及非酒精中毒对照组。
在按ADH2、ADH3和ALDH2的相关基因型分层后，中国汉族人群中DRD2基因座的遗传变异与酒精中毒之间不存在显著关联。
