Investigation of the functional effect of monoamine oxidase polymorphisms in human brain

Balciuniene, Jorune; Emilsson, Lina; Oreland, Lars; Pettersson, Ulf; Jazin, Elena

doi:10.1007/s00439-001-0652-8

Cited by 155 publications

(134 citation statements)

References 47 publications

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“…Therefore, other functional loci might partially or totally account for MAOA-LPR functional effect. In line with this idea, two recent studies evaluating mRNA expression of MAOA in human brain 28,44 and MAOA activity 44 suggest that not all the variance in MAOA activity/transcription due to genetic factors is explained by MAOA-LPR and other functional loci may play a role. For this reason, we genotyped nine additional SNPs encompassing the region where both MAOA and MAOB genes are located.…”

Section: Discussionmentioning

confidence: 91%

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P = 0.005), particularly antisocial alcoholism (P = 0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P = 0.008) and antisocial alcoholics (P = 0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P = 0.006), and to a lesser extent with antisocial alcoholism (P = 0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.

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Section: Discussionmentioning

confidence: 91%

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

et al. 2007

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“…For example, normalized MAO A specific activity from the high MAO A genotype has been reported to be significantly higher than that for the low MAO A genotype in human fibroblast cultures (Denney et al 1999). In contrast, a direct assay of A from cortical autopsy samples from 31 human subjects did not find a significant association of any single MAO A polymorphism with expression levels of MAO A (Balciuniene et al 2002). Whether the high and low MAO A genotypes (which are defined in terms of their respective transcriptional activities) are associated with differences in MAO A (the gene product) has not been determined in vivo, however.…”

Section: Discussionmentioning

confidence: 95%

Evidence That Brain MAO A Activity Does Not Correspond to MAO A Genotype in Healthy Male Subjects

Fowler

Alia‐Klein

Kriplani

et al. 2007

Biological Psychiatry

106

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“…Although a functional effect of MAOA-LPR has been demonstrated in cell lines 12,14 and human fibroblasts, 13 its effect on MAOA mRNA and MAOA protein levels in human post-mortem brain tissue appears to be very weak and insignificant. 49 In the Balciuniene et al 40 study, a haplotype composed of the low activity MAOA-LPR 3 repeat allele and a SNP from an intronic region in MAOB was significantly associated with decreased MAOA function, whereas other MAOA-LPR/MAOB SNP haplotypes containing the MAOA-LPR 3 repeat allele were associated with higher expression.…”

Section: Discussionmentioning

confidence: 96%

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

Ducci¹,

Newman²,

Funt³

et al. 2006

Mol Psychiatry

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Variation in brain monoaminergic activity is heritable and modulates risk of alcoholism and other addictions, as well as food intake and energy expenditure. Monoamine oxidase A deaminates the monoamine neurotransmitters serotonin, dopamine (DA), and noradrenalin. The monoamine oxidase A (MAOA) gene (Xp11.5) contains a length polymorphism in its promoter region (MAOA-LPR) that putatively affects transcriptional efficiency. Our goals were to test (1) whether MAOA-LPR contributes to interindividual variation in monoamine activity, assessed using levels of cerebrospinal fluid (CSF) monoamine metabolites; and (2) whether MAOA-LPR genotype influences alcoholism and/or body mass index (BMI). Male, unrelated criminal alcoholics (N = 278) and controls (N = 227) were collected from a homogeneous Finnish source population. CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were available from 208 participants. Single allele, hemizygous genotypes were grouped according to inferred effect of the MAOA alleles on transcriptional activity. MAOA-LPR genotypes had a significant effect on CSF HVA concentration (P = 0.01) but explained only 3% of the total variance. There was a detectable but nonsignificant genotype effect on 5-HIAA and no effects on MHPG. Specifically, the genotype conferring high MAOA activity was associated with lower HVA levels in both alcoholics and controls, a finding that persisted after accounting for the potential confounds of alcoholism, BMI, height, and smoking. MAOA-LPR genotype predicted BMI (P < 0.005), with the high-activity genotype being associated with lower BMI. MAOA-LPR genotypes were not associated with alcoholism or related psychiatric phenotypes in this data set. Our results suggest that MAOA-LPR allelic variation modulates DA turnover in the CNS, but does so in a manner contrary to our prior expectation that alleles conferring high activity would predict higher HVA levels in CSF. Our results are consistent with an emerging literature that suggests greater complexity in how variation in MAOA expression alters monoaminergic function. Finally, our work suggests that MAOA may be involved in the regulation of BMI. Independent samples are necessary to confirm this preliminary finding.

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Investigation of the functional effect of monoamine oxidase polymorphisms in human brain

Cited by 155 publications

References 47 publications

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Evidence That Brain MAO A Activity Does Not Correspond to MAO A Genotype in Healthy Male Subjects

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

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