The in vitro functional analysis of single-nucleotide polymorphisms associated with growth hormone (GH) response in children with GH deficiency.
Pharmacogenomics J
; 19(2): 200-210, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-29855605
ABSTRACT
Response to recombinant human growth hormone (r-hGH) in the first year of therapy has been associated with single-nucleotide polymorphisms (SNPs) in children with GH deficiency (GHD). Associated SNPs were screened for regulatory function using a combination of in silico techniques. Four SNPs in regulatory sequences were selected for the analysis of in vitro transcriptional activity (TA). There was an additive effect of the alleles in the four genes associated with good growth response. For rs3110697 within IGFBP3, rs1045992 in CYP19A1 and rs2888586 in SOS1, the variant associated with better growth response showed higher TA with r-hGH treatment. For rs1024531 in GRB10, a negative regulator of IGF-I signalling and growth, the variant associated with better growth response had a significantly lower TA on r-hGH stimulation. These results indicate that specific SNP variants have effects on TA that provide a rationale for their clinical impact on growth response to r-hGH therapy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Hormona del Crecimiento
/
Aromatasa
/
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
/
Proteína SOS1
/
Trastornos del Crecimiento
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido