Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse

Abstract

Abnormalities in monoamine oxidase (MAO) levels have been implicated in a wide range of psychiatric disorders. We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effect? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were divided into four groups of increasing size. There was a significant association between the MAOA gene and behavioral phenotypes in both groups, and in both the longest alleles were associated with the greatest phenotypic effect. The strongest effect was for the diagnosis of drug dependence (P = 0.00003). The VNTR allele groups were in significant linkage disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent with the possibility that different-sized alleles of the short-repeat polymorphisms themselves may play a role in gene regulation, further studies directly linking these alleles with enzyme levels need to be done.

Antisocial alcoholism and serotonin-related polymorphisms: association tests

“…Early-onset alcohol dependence with antisocial traits has consistently been reported to be associated with MAOA alleles that imply low MAO activity: MAOA (CA) n , Parsian et al (1995); MAOA (VNTR), Gade et al (1998); MAOA (T1460C), Parsian (1999) and Parsian and Cloninger (2001); MAOA-LPR, Samochowiec et al (1999). Gade et al (1998) found one VNTR allele to be more frequent in substance-dependent patients (a group that may have AAL characteristics), compared with purely alcohol-dependent patients. However, in adolescent patients with early onset substance abuse, the longer repeat alleles (> 115) of MAOA (CA) n , were nonsignificantly higher than for controls (Vanyukov et al, 1995).…”

“…For an AAL subtype, Parsian (1999) verified case-control differences in haplotypes of MAOA by testing a small sam-ple of mothers by the transmission disequilibrium test. Gade et al (1998) found one VNTR allele to be higher for substance abuse patients, compared with alcohol-dependent patients. In addition, a functional 30 base pair repeat polymorphism in the promoter of MAOA was recently reported to be associated with AAL (Samochowiec et al, 1999).…”

Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity

“…In addition, the MAOA-LPR has been associated with bipolar disorders particularly in females (Ho et al, 2000), and with suicide in depressed males (Du et al, 2002), whereas other studies failed to detect association with suicidal behavior in mood disorders (Kunugi et al, 1999;Kirov et al, 1999;Syagailo et al, 2001;Ono et al, 2002). Although not consistently replicated (Craddock et al, 1995;Nothen et al, 1995), various other MAOA variations were found to influence addictive behavior (Parsian et al, 1995;Vanyukov et al, 1995;Hsu et al, 1996;Gade et al, 1998) and the risk for affective und anxiety disorders (Schulze et al, 2000;Deckert et al, 1999;Furlong et al, 1999). Finally, recent work focusing on both genetic and early environmental factors has begun to untangle expected complex relationships by demonstrating an interaction of MAOA-LPR genotype and adverse childhood environment modulating the risk for both conduct disorder and impulsive traits, antisocial behavior, aggressiveness, and violence in adulthood (Caspi et al, 2002;Foley et al, 2004;Huang et al, 2004).…”

A Regulatory Monoamine Oxidase A Promoter Polymorphism and Personality Traits

“…Xp21-p11 [5]. The MAOA gene has previously been associated with psychiatric conditions and deviant behaviour [6][7][8]. In 1993, a rare mutation in the MAOA gene was reported to be associated with abnormal behaviour among men in a Dutch family [9].…”