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Göteborgs universitets publikationer

Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.

Författare och institution:
Eleni Aklillu (-); Sara Karlsson (-); Olof Zachrisson (Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi); Vural Ozdemir (-); Hans Ågren (Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi)
Publicerad i:
Pharmacogenetics and genomics, 19 ( 4 ) s. 267-75
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
OBJECTIVE: Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. METHODS: In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. RESULTS: AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. CONCLUSION: The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Case-Control Studies, Depression, cerebrospinal fluid, diagnosis, genetics, Dopamine, cerebrospinal fluid, European Continental Ancestry Group, genetics, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Hydroxyindoleacetic Acid, cerebrospinal fluid, Logistic Models, Male, Methoxyhydroxyphenylglycol, cerebrospinal fluid, Models, Biological, Monoamine Oxidase, cerebrospinal fluid, genetics, Polymorphism, Genetic, Promoter Regions, Genetic, Scandinavia, Sex Factors
Postens nummer:
Posten skapad:
2009-09-29 17:03
Posten ändrad:
2009-09-29 21:47

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