CORRELATION OF LENGTH OF VNTR ALLELES AT THE X-LINKED MAOA GENE AND PHENOTYPIC EFFECT IN TOURETTE-SYNDROME AND DRUG-ABUSE

Abnormalities in monoamine oxidase (MAO) levels have been implicated i n a wide range of psychiatric disorders. We have examined a VNTR polym orphism at the X-linked MAOA gene to test two hypotheses: (1) Do varia nts of the MAOA gene play a role in any of the behavioral disorders as sociated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effe ct? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were di vided into four groups of increasing size. There was a significant ass ociation between the MAOA gene and behavioral phenotypes in both group s, and in both the longest alleles were associated with the greatest p henotypic effect. The strongest effect was for the diagnosis of drug d ependence (P=0.00003). The VNTR allele groups were in significant link age disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent wi th the possibility that different-sized alleles of the short-repeal po lymorphisms themselves may play a role in gene regulation, further stu dies directly linking these alleles with enzyme levels need to be done .