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Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population
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2006 (English)In: Archives of General Psychiatry, ISSN 0003-990X, E-ISSN 1538-3636, Vol. 63, no 10, 1103-1110 p.Article in journal (Refereed) Published
Abstract [en]

CONTEXT: Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin (5-HT) biosynthetic pathway responsible for the regulation of serotonin levels. Tryptophan hydroxylase 2 (TPH2) was found to be solely expressed in the brain and therefore considered an important susceptibility gene in psychiatric disorders.

OBJECTIVE: To determine the role of the brain-specific TPH2 gene in unipolar (UP) disorder and bipolar (BP) disorder in a northern Swedish, isolated population.

DESIGN: HapMap-based haplotype-tagging single nucleotide polymorphism (htSNP) patient-control association study.

SETTING: A northern Swedish, isolated population.

PARTICIPANTS: One hundred thirty-five unrelated patients with UP disorder, 182 unrelated patients with BP disorder, and 364 unrelated control individuals.

RESULTS: Significant allelic association was identified in our UP disorder association sample for an htSNP located in the 5' promoter region (rs11178997; P = .001). Haplotype analysis supported this significant result by the presence of a protective factor on hapblock 2 (P(specific) = .002). In the BP disorder association sample, single-marker association identified a significant htSNP in the upstream regulatory region (rs4131348; P = .004). Moreover, haplotype analysis in the BP disorder sample showed that the same htSNPs from hapblock 2 associated with UP disorder were also significantly associated with BP disorder (P(specific) = .002).

CONCLUSIONS: Haplotype-based analysis of TPH2 in patients with UP and BP disorder and controls from northern Swedish descent provides preliminary evidence for protective association in both disorders and thus supports a central role for TPH2 in the pathogenesis of affective disorders.

Place, publisher, year, edition, pages
American Medical Association , 2006. Vol. 63, no 10, 1103-1110 p.
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URN: urn:nbn:se:umu:diva-87605DOI: 10.1001/archpsyc.63.10.1103PubMedID: 17015812OAI: diva2:710224
Available from: 2014-04-05 Created: 2014-04-05 Last updated: 2015-12-07

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Norrback, Karl-FredrikAdolfsson, Rolf
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