Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls.

Brunner et al. (1993, Science 262, 578-580) reported a family in which several males were affected by a syndrome of borderline mental retardation and abnormal behavior. Sequencing of exon 8 of the MAO-A gene revealed a mutation that results in a termination codon and was associated with the syndrome in the family. To determine the possible role of any mutation in exon 8 of the MAO-A gene in susceptibility to alcoholism associated with antisocial personality (ASP), we sequenced genomic DNA from 50 alcoholics and 50 normal controls. We detected only the point mutation at the position 941 (T --> G). Additional samples of alcoholics and normal controls were also screened for this mutation and the mutation in exon 14 by PCR assays. Comparison of alcoholics with ASP to normal controls for both mutation frequencies in exons 8 and 14 was positive. However, the haplotype frequency differences in the above groups were borderline significant. The most common haplotype between these mutations and a (CA)n repeat marker in the gene was F1E,C6. The frequency differences between alcoholics with ASP and normal controls for this haplotype were significant (P = 0.033). In TDT analysis, comparison of the overall haplotypes, transmitted to nontransmitted, was borderline significant. These data indicate that mutations in the MAO-A gene may play a role in the development of alcoholism associated with ASP.