Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.
Am J Epidemiol
; 175(9): 867-77, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22494952
ABSTRACT
Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability = 0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95% credible interval (CrI) 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI 0.10, 0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Hormônio do Crescimento Humano
/
Transtornos do Crescimento
/
Modelos Genéticos
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Child
/
Humans
Idioma:
En
Revista:
Am J Epidemiol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido