A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome

Autores
Clayton, P.; Chatelain, P.; Tato, L.; Yoo, H. W.; Ambler, G. R.; Belgorosky, Alicia; Quinteiro, S.; Deal, C.; Stevens, A.; Raelson, J.; Croteau, P.; Destenaves, B.; Olivier, C.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design: A prospective, multicenter, international, open-label pharmacogenomic study. Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.
Fil: Clayton, P.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido
Fil: Chatelain, P.. Université Claude Bernard. Hopital Mère-Enfant. Département Pediatrie; Francia
Fil: Tato, L.. Università degli Studi di Verona. Clinica Pediatrica; Italia
Fil: Yoo, H. W.. University of Ulsan. College of Medicine. Asan Medical Center. Department of Pediatrics; Corea del Sur
Fil: Ambler, G. R.. University of Sydney. The Children’s Hospital at Westmead; Australia
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Quinteiro, S.. Hospital Materno Infantil. Servicio de Pediatría Endocrino; España
Fil: Deal, C.. University of Montreal. Department of Pediatrics; Canadá
Fil: Stevens, A.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido
Fil: Raelson, J.. Genizon BioSciences; Canadá
Fil: Croteau, P.. Genizon BioSciences; Canadá
Fil: Destenaves, B.. Merck Serono S.A.; Suiza
Fil: Olivier, C.. Merck Serono S.A; Suiza
Materia
GHR
Turner Syndrome
GH deficiency
rhGHsensitivity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/3723
Acceder
id CONICETDig_c9c4241373738c7a6cdd5683aab608bd
oai_identifier_str oai:ri.conicet.gov.ar:11336/3723
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndromeClayton, P.Chatelain, P.Tato, L.Yoo, H. W.Ambler, G. R.Belgorosky, AliciaQuinteiro, S.Deal, C.Stevens, A.Raelson, J.Croteau, P.Destenaves, B.Olivier, C.GHRTurner SyndromeGH deficiencyrhGHsensitivityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design: A prospective, multicenter, international, open-label pharmacogenomic study. Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.Fil: Clayton, P.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino UnidoFil: Chatelain, P.. Université Claude Bernard. Hopital Mère-Enfant. Département Pediatrie; FranciaFil: Tato, L.. Università degli Studi di Verona. Clinica Pediatrica; ItaliaFil: Yoo, H. W.. University of Ulsan. College of Medicine. Asan Medical Center. Department of Pediatrics; Corea del SurFil: Ambler, G. R.. University of Sydney. The Children’s Hospital at Westmead; AustraliaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Quinteiro, S.. Hospital Materno Infantil. Servicio de Pediatría Endocrino; EspañaFil: Deal, C.. University of Montreal. Department of Pediatrics; CanadáFil: Stevens, A.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino UnidoFil: Raelson, J.. Genizon BioSciences; CanadáFil: Croteau, P.. Genizon BioSciences; CanadáFil: Destenaves, B.. Merck Serono S.A.; SuizaFil: Olivier, C.. Merck Serono S.A; SuizaBioscientifica2013-06-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3723Clayton, P.; Chatelain, P.; Tato, L.; Yoo, H. W.; Ambler, G. R.; et al.; A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome; Bioscientifica; European Journal of Endocrinology; 169; 12-6-2013; 277-2890804-4643enginfo:eu-repo/semantics/altIdentifier/url/http://www.eje-online.org/content/169/3/277.longinfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731924/info:eu-repo/semantics/altIdentifier/issn/0804-4643info:eu-repo/semantics/altIdentifier/doi/10.1530%2FEJE-13-0069info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:55:38Zoai:ri.conicet.gov.ar:11336/3723instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:55:38.915CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
title A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
spellingShingle A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
Clayton, P.
GHR
Turner Syndrome
GH deficiency
rhGHsensitivity
title_short A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
title_full A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
title_fullStr A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
title_full_unstemmed A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
title_sort A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome
dc.creator.none.fl_str_mv Clayton, P.
Chatelain, P.
Tato, L.
Yoo, H. W.
Ambler, G. R.
Belgorosky, Alicia
Quinteiro, S.
Deal, C.
Stevens, A.
Raelson, J.
Croteau, P.
Destenaves, B.
Olivier, C.
author Clayton, P.
author_facet Clayton, P.
Chatelain, P.
Tato, L.
Yoo, H. W.
Ambler, G. R.
Belgorosky, Alicia
Quinteiro, S.
Deal, C.
Stevens, A.
Raelson, J.
Croteau, P.
Destenaves, B.
Olivier, C.
author_role author
author2 Chatelain, P.
Tato, L.
Yoo, H. W.
Ambler, G. R.
Belgorosky, Alicia
Quinteiro, S.
Deal, C.
Stevens, A.
Raelson, J.
Croteau, P.
Destenaves, B.
Olivier, C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GHR
Turner Syndrome
GH deficiency
rhGHsensitivity
topic GHR
Turner Syndrome
GH deficiency
rhGHsensitivity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design: A prospective, multicenter, international, open-label pharmacogenomic study. Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.
Fil: Clayton, P.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido
Fil: Chatelain, P.. Université Claude Bernard. Hopital Mère-Enfant. Département Pediatrie; Francia
Fil: Tato, L.. Università degli Studi di Verona. Clinica Pediatrica; Italia
Fil: Yoo, H. W.. University of Ulsan. College of Medicine. Asan Medical Center. Department of Pediatrics; Corea del Sur
Fil: Ambler, G. R.. University of Sydney. The Children’s Hospital at Westmead; Australia
Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Quinteiro, S.. Hospital Materno Infantil. Servicio de Pediatría Endocrino; España
Fil: Deal, C.. University of Montreal. Department of Pediatrics; Canadá
Fil: Stevens, A.. Royal Manchester Children’s Hospital. Manchester Academic Health Sciences Centre; Reino Unido
Fil: Raelson, J.. Genizon BioSciences; Canadá
Fil: Croteau, P.. Genizon BioSciences; Canadá
Fil: Destenaves, B.. Merck Serono S.A.; Suiza
Fil: Olivier, C.. Merck Serono S.A; Suiza
description Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design: A prospective, multicenter, international, open-label pharmacogenomic study. Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.
publishDate 2013
dc.date.none.fl_str_mv 2013-06-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/3723
Clayton, P.; Chatelain, P.; Tato, L.; Yoo, H. W.; Ambler, G. R.; et al.; A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome; Bioscientifica; European Journal of Endocrinology; 169; 12-6-2013; 277-289
0804-4643
url http://hdl.handle.net/11336/3723
identifier_str_mv Clayton, P.; Chatelain, P.; Tato, L.; Yoo, H. W.; Ambler, G. R.; et al.; A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome; Bioscientifica; European Journal of Endocrinology; 169; 12-6-2013; 277-289
0804-4643
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.eje-online.org/content/169/3/277.long
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731924/
info:eu-repo/semantics/altIdentifier/issn/0804-4643
info:eu-repo/semantics/altIdentifier/doi/10.1530%2FEJE-13-0069
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bioscientifica
publisher.none.fl_str_mv Bioscientifica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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