Allelic polymorphism in the serotonin transporter gene in major depression patients

Introduction: Major depression (MD), like other mood disorders, is considered a worldwide endemic pathology, becoming one of the biggest public health problems. The hereditary factors of mood disorders have been studied for many years and different chromosomal regions and genes have been involved in...

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Autores:
Escobar, Carlos H.
Calderón, Jorge Hernán
Moreno, Germán Alberto
Tipo de recurso:
Article of journal
Fecha de publicación:
2011
Institución:
Fundación Universitaria de Ciencias de la Salud - FUCS
Repositorio:
Repositorio Digital Institucional ReDi
Idioma:
eng
spa
OAI Identifier:
oai:repositorio.fucsalud.edu.co:001/1343
Acceso en línea:
https://doi.org/10.25100/cm.v42i1.750
https://repositorio.fucsalud.edu.co/handle/001/1343
Palabra clave:
Major depression
5-HTTLPR
VNTR
Colombia
Trastorno depresivo mayor
Cristalización
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
id FUCS2_938f0756106563b79e37a7307e1f411a
oai_identifier_str oai:repositorio.fucsalud.edu.co:001/1343
network_acronym_str FUCS2
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repository_id_str
dc.title.eng.fl_str_mv Allelic polymorphism in the serotonin transporter gene in major depression patients
title Allelic polymorphism in the serotonin transporter gene in major depression patients
spellingShingle Allelic polymorphism in the serotonin transporter gene in major depression patients
Major depression
5-HTTLPR
VNTR
Colombia
Trastorno depresivo mayor
Cristalización
title_short Allelic polymorphism in the serotonin transporter gene in major depression patients
title_full Allelic polymorphism in the serotonin transporter gene in major depression patients
title_fullStr Allelic polymorphism in the serotonin transporter gene in major depression patients
title_full_unstemmed Allelic polymorphism in the serotonin transporter gene in major depression patients
title_sort Allelic polymorphism in the serotonin transporter gene in major depression patients
dc.creator.fl_str_mv Escobar, Carlos H.
Calderón, Jorge Hernán
Moreno, Germán Alberto
dc.contributor.author.none.fl_str_mv Escobar, Carlos H.
Calderón, Jorge Hernán
Moreno, Germán Alberto
dc.subject.proposal.eng.fl_str_mv Major depression
5-HTTLPR
VNTR
topic Major depression
5-HTTLPR
VNTR
Colombia
Trastorno depresivo mayor
Cristalización
dc.subject.proposal.spa.fl_str_mv Colombia
dc.subject.decs.none.fl_str_mv Trastorno depresivo mayor
Cristalización
description Introduction: Major depression (MD), like other mood disorders, is considered a worldwide endemic pathology, becoming one of the biggest public health problems. The hereditary factors of mood disorders have been studied for many years and different chromosomal regions and genes have been involved in this physiopathological process. Objective: To establish the association between allelic variants of the serotonin transporter gene (5-HTTLPR and VNTR) and MD in a population with this diagnostic in the department of Caldas, Colombia. Materials and methods: A case-control study was conducted with individuals older than 16 years of age born in the department of Caldas. The sample was composed of 59 patients with the MD with family antecedents of the pathology and 59 controls paired by precedence, age, and gender. For the cases and controls selection the Diagnostic Interview for Genetic Studies (DIGS) was used. Using the Hranilovic et al. protocol, the polymorphic regions in the promoter and third intron of the Serotonin Transporter gene was amplified. Results: It was not possible to find association between MD and the genetic or clinical variables. The absence of the short allele of the promoter could act as a protective factor (OR=0.70 CI 95%=0.313 to 1.604), for the development of the pathology in this population, and the presence of at least one copy of the 10 repetition alleles of the third intron could act as a risk factor (OR: 1.25), but the wide confidence interval (CI 95%=0.38 to 2.64) does not permit supporting these conclusions. Discussion: The results obtained in this population do not yield conclusive information related with the etiopathogeny of MD, but do not contradict those obtained in other studies with bigger samples than ours. The broad confidence interval does not support conclusions about the role as a risk factor for the 10 repetition alleles of the intron or the absence of the S allele of the promoter as a protector factor. Further studies with larger population samples may help to clarify these facts.
publishDate 2011
dc.date.issued.none.fl_str_mv 2011-04-11
dc.date.accessioned.none.fl_str_mv 2021-02-16T21:10:38Z
dc.date.available.none.fl_str_mv 2021-02-16T21:10:38Z
dc.type.spa.fl_str_mv Artículo de revista
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url https://doi.org/10.25100/cm.v42i1.750
https://repositorio.fucsalud.edu.co/handle/001/1343
dc.language.iso.spa.fl_str_mv eng
spa
language eng
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dc.relation.ispartof.none.fl_str_mv Colombia Médica ISSN: 1657-9534 Vol. 42 Núm.1 (2011)
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dc.relation.ispartofjournal.spa.fl_str_mv Colombia Médica
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dc.rights.creativecommons.spa.fl_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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eu_rights_str_mv openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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dc.publisher.place.spa.fl_str_mv Calí : Universidad del Valle
dc.source.spa.fl_str_mv http://colombiamedica.univalle.edu.co/index.php/comedica/article/view/750
institution Fundación Universitaria de Ciencias de la Salud - FUCS
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spelling Escobar, Carlos H.3ebe2202244078d44a29f5abeb928a9cCalderón, Jorge Hernán381eb520dacd6096af12e4dbabcf76c5Moreno, Germán Albertoad7139628001a7873309b092f218dd032021-02-16T21:10:38Z2011-04-112021-02-16T21:10:38ZIntroduction: Major depression (MD), like other mood disorders, is considered a worldwide endemic pathology, becoming one of the biggest public health problems. The hereditary factors of mood disorders have been studied for many years and different chromosomal regions and genes have been involved in this physiopathological process. Objective: To establish the association between allelic variants of the serotonin transporter gene (5-HTTLPR and VNTR) and MD in a population with this diagnostic in the department of Caldas, Colombia. Materials and methods: A case-control study was conducted with individuals older than 16 years of age born in the department of Caldas. The sample was composed of 59 patients with the MD with family antecedents of the pathology and 59 controls paired by precedence, age, and gender. For the cases and controls selection the Diagnostic Interview for Genetic Studies (DIGS) was used. Using the Hranilovic et al. protocol, the polymorphic regions in the promoter and third intron of the Serotonin Transporter gene was amplified. Results: It was not possible to find association between MD and the genetic or clinical variables. The absence of the short allele of the promoter could act as a protective factor (OR=0.70 CI 95%=0.313 to 1.604), for the development of the pathology in this population, and the presence of at least one copy of the 10 repetition alleles of the third intron could act as a risk factor (OR: 1.25), but the wide confidence interval (CI 95%=0.38 to 2.64) does not permit supporting these conclusions. Discussion: The results obtained in this population do not yield conclusive information related with the etiopathogeny of MD, but do not contradict those obtained in other studies with bigger samples than ours. The broad confidence interval does not support conclusions about the role as a risk factor for the 10 repetition alleles of the intron or the absence of the S allele of the promoter as a protector factor. Further studies with larger population samples may help to clarify these facts.Introducción: La depresión mayor (DM), como los demás trastornos del estado de ánimo, es considerada un síndrome endémico en el contexto mundial. Por ello se ha constituido en uno de los más grandes problemas de salud pública. Los factores hereditarios de los trastornos del estado de ánimo han sido estudiados por muchos años y en su proceso fisiopatológico se han involucrado diferentes porciones cromosómicas y genes. Objetivo: Establecer la asociación entre las variantes alélicas del gen del transportador de serotonina (5-HTTLPR y VNTR) y la DM, en una población con este diagnóstico en el departamento de Caldas, Colombia. Materiales y métodos: Se realizó un estudio de casos y controles en personas mayores de 16 años originarias del departamento de Caldas. La muestra incluyó 59 pacientes con el síndrome y antecedentes familiares de DM y 59 sujetos controles pareados por procedencia, edad y género. Para laselección de los casos y controles se utilizó el instrumento Diagnostic Interview for Genetic Studies (DIGS). Se usó el protocolo de Hranilovic et al.., se amplificaron las porciones polimórficas del promotor y el tercer intrón del gen del transportador de serotonina. Resultados: No se encontró asociación entre l a D M y las variables clínicas o genéticas. La ausencia del alelo corto del promotor podría actuar como factor protector (OR=0.70 IC95%= 0.313 a 1.604), para el desarrollo de este síndrome en la población colombiana y la presencia de al menos una copia del alelo de 10 repeticiones del tercer intrón, podría actuar como factor de riesgo (OR: 1,25), pero el amplio intervalo deconfianza (IC 95%=0.38 a 2.64) no otorga soporte para estas afirmaciones. Discusión: Los resultados obtenidos con la presente población no entregan información concluyente relacionada con la etiopatogenia de la DM, pero tampoco riñen con los obtenidos en estudios similares con muestras de mayor tamaño. La amplitud de los intervalos de confianza no permiten emitir conclusiones definitivas acerca de factores de riesgo (alelo 10 del intrón) o protectores (ausencia delalelo S del promotor). Se requieren estudios con muestras más grandes que otorguen mayor precisión y poder a estos resultadoshttp://colombiamedica.univalle.edu.co/index.php/comedica/article/view/7506 p.application/pdfAllelic polymorphism in the serotonin transporter gene in major depression patientsArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_8042info:eu-repo/semantics/workingPaperinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/coar/version/c_970fb48d4fbd8a85https://doi.org/10.25100/cm.v42i1.750https://repositorio.fucsalud.edu.co/handle/001/1343engspaColombia Médica ISSN: 1657-9534 Vol. 42 Núm.1 (2011)5314842Colombia Médicainfo:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)http://purl.org/coar/access_right/c_abf2Major depression5-HTTLPRVNTRColombiaTrastorno depresivo mayorCristalizaciónCalí : Universidad del VallePublicationORIGINALAllelic polymorphism in the serotonin transporter gene in major 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