Bipolar Research Today is a free monthly online journal that collates and summarizes the latest research about Bipolar, including details on bipolar disorder, symptoms, treatment, depression, medication. | ||||||||
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Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population.Van Den Bogaert A, Sleegers K, De Zutter S, Heyrman L, Norrback KF, Adolfsson R, Van Broeckhoven C, Del-Favero J Applied Molecular Genomics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium. 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. Published 3 October 2006 in Arch Gen Psychiatry, 63(10): 1103-10.
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