Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a northern Swedish, isolated population

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Abstract

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 (Pspecific = .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 (Pspecific = .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. ©2006 American Medical Association. All rights reserved.

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Van Den Bogaert, A., Sleegers, K., De Zutter, S., Heyrman, L., Norrback, K. F., Adolfsson, R., … Del-Favero, J. (2006). Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a northern Swedish, isolated population. Archives of General Psychiatry, 63(10), 1103–1110. https://doi.org/10.1001/archpsyc.63.10.1103

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