Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder
OBJECTIVE: A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. METHOD: Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview ((R)). RESULTS: Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION: Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.
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Associação Brasileira de Psiquiatria
2011
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oai:scielo:S1516-444620110002000142013-04-09Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorderRocha,Felipe Filardi daAlvarenga,Nathália BuenoLage,Naira VassaloRomano-Silva,Marco AurélioMarco,Luiz Armando deCorrêa,Humberto Psychiatry Obsessive-compulsive disorder Polymorphism, genetic Tryptophan hydroxylase Haplotypes OBJECTIVE: A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. METHOD: Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview ((R)). RESULTS: Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION: Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.info:eu-repo/semantics/openAccessAssociação Brasileira de PsiquiatriaBrazilian Journal of Psychiatry v.33 n.2 20112011-06-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462011000200014en10.1590/S1516-44462011005000003 |
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Rocha,Felipe Filardi da Alvarenga,Nathália Bueno Lage,Naira Vassalo Romano-Silva,Marco Aurélio Marco,Luiz Armando de Corrêa,Humberto |
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Rocha,Felipe Filardi da Alvarenga,Nathália Bueno Lage,Naira Vassalo Romano-Silva,Marco Aurélio Marco,Luiz Armando de Corrêa,Humberto Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
author_facet |
Rocha,Felipe Filardi da Alvarenga,Nathália Bueno Lage,Naira Vassalo Romano-Silva,Marco Aurélio Marco,Luiz Armando de Corrêa,Humberto |
author_sort |
Rocha,Felipe Filardi da |
title |
Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
title_short |
Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
title_full |
Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
title_fullStr |
Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
title_full_unstemmed |
Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
title_sort |
associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder |
description |
OBJECTIVE: A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. METHOD: Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview ((R)). RESULTS: Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION: Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder. |
publisher |
Associação Brasileira de Psiquiatria |
publishDate |
2011 |
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http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462011000200014 |
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