Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees.

Abstract:

OBJECTIVE:Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin biosynthetic pathway and plays an important role in the regulation of serotonin levels. Recently, a brain-specific isoform, tryptophan hydroxylase 2 or n-tryptophan hydroxylase, has been discovered. Some studies reported genetic and functional associations between this isoform and bipolar disorder and/or major depressive disorder. The aim of this study was to investigate further association of genetic variants in French Canadian samples with bipolar disorders. METHODS:Genetic variants in the tryptophan hydroxylase 2 gene were genotyped in a case-control sample consisting of 225 affected individuals (191 bipolar I and 34 bipolar II) and 221 controls and in a collection of extended pedigrees and trios from the same population 357 nuclear families (201 bipolar I, 64 bipolar II, 79 recurrent major depressive disorder). RESULTS:We determined linkage disequilibrium structure in our isolated population and analyzed six tagged single nucleotide polymorphisms in the case-control sample. Whereas no single, single nucleotide polymorphism gave any significant result, a three single nucleotide polymorphism haplotype gave a global P=0.01. Family-based association showed significant association (P=0.004) of one polymorphism (rs4290270) with the major allele overtransmitted to affected offspring. CONCLUSIONS:Case-control and family-based association studies further support the presence of a susceptibility locus for bipolar disorder in tryptophan hydroxylase 2 by showing statistically significant associations with both, single nucleotide polymorphism alone and haplotype of single nucleotide polymorphism markers.

journal_name

Psychiatr Genet

journal_title

Psychiatric genetics

authors

Harvey M,Gagné B,Labbé M,Barden N

doi

10.1097/YPG.0b013e3280111877

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

17-22

issue

1

eissn

0955-8829

issn

1473-5873

pii

00041444-200702000-00008

journal_volume

17

pub_type

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