Lack of association between alcoholism and alleles in the δ-aminolevulinic acid dehydratase (ALAD) gene

δ-Aminolevulinic acid dehydratase (ALAD) is the second enzyme in the heme biosynthetic pathway and catalyzes two molecules of δ-aminolevulinate (ALA), which is a potent agonist for GABA autoreceptors. ALAD has two common alleles and thus consists of three distinct isozymes, designated 1-1, 1-2, and 2-2. It has been shown recently that ALAD¹ allele is associated with alcoholic liver injury. This association was ascribed to possible differences among isozymes in sensitivity to oxidized glutathione (GSSG), and this sensitivity is increased in erythrocytes of alcoholic patients. In the present study we measured erythrocyte ALAD activity from subjects with different ALAD genotype and found ALAD1-1 is most sensitive to GSSG. We then investigated allele frequencies of ALAD in alcoholics (n = 126) and healthy controls (n = 115). For the control group, the frequencies were 0.94 (ALAD¹) and 0.06 (ALAD²) and for the overall alcoholic group, 0.91 (ALAD¹) and 0.09 (ALAD²). There were no significant differences in allele frequencies at the ALAD locus between the two groups. Subtyping the alcoholics according to the presence or absence of delirium tremens, hallucinosis, withdrawal seizure or liver cirrhosis failed to show statistically significant differences in the allele frequencies. We conclude that our data do not support the evidence of an allelic association between the ALAD¹ and alcoholism.