Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees
| Autor: | Bernard Gagné, Nicholas Barden, Mario Harvey, Michel Labbé |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Canada Linkage disequilibrium Bipolar Disorder Genotype Population Single-nucleotide polymorphism Tryptophan Hydroxylase Biology Polymorphism Single Nucleotide Genetics medicine Humans Genetic Predisposition to Disease Bipolar disorder education Biological Psychiatry Genetics (clinical) Genetic association Neurons education.field_of_study Haplotype Tryptophan hydroxylase medicine.disease Pedigree Psychiatry and Mental health Case-Control Studies Major depressive disorder Female France |
| Zdroj: | Psychiatric Genetics. 17:17-22 |
| ISSN: | 0955-8829 |
| DOI: | 10.1097/ypg.0b013e3280111877 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|