No association between DRD2 locus and alcoholism after controlling the ADHand 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 diffe rent genotypes at the genes encoding the enzymes involved in alcohol metabo lism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial ald ehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males (Tho masson et al., 1991; Chen WJ ct al., 1996; Chen CC et al., unpublished data ). Therefore, association studies of alcoholism in Chinese Han might be mor e sensitive if controlled for the genotypes of ADH2,ADH3, and ALDH2, when o ther 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 nonalco holics) 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 stratif ications by ADH and ALDH2 genotypes were examined; no genotypes or haplotyp es at DRD2 differ between alcoholics and nonalcoholics except for a small n umber of nominally significant p-values which do not constitute significant results given the many tests done, some of which are not independent of on e another due to linkage disequilibrium. These tests included considering t he high risk (ADH2*1/*1; *1/*2; ADH3*1/*2; *2/*2; and ALDH2*1/*1) and the l ow risk (ADH2*2/*2; ADH3*1/*1; and ALDH2*1/*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.