No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population.

BACKGROUND

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to the development of alcoholism in Chinese Han males (Thomasson et al., 1991; Chen WJ et al., 1996; Chen CC et al., unpublished data).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.

METHODS

We studied 213 Chinese Han subjects (128 alcoholics and 85 nonalcoholics) with alcohol dependence defined according to DSM-III-R criteria.

RESULTS

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.

CONCLUSIONS

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.