Growth hormone receptor polymorphism and growth hormone therapy response in children: A bayesian meta-analysis

Research output: Contribution to journalArticle

  • External authors:
  • Mattea Solomon
  • Marcel Zwahlen
  • Reena Morjaria
  • Laura Audí
  • Gerhard Binder
  • Werner Blum
  • Pierre Bougnres
  • Christine Dos Santos
  • Antonio Carrascosa
  • Anita Hokken-Koelega
  • Alexander Jorge
  • Primus E. Mullis
  • Maïthé Tauber
  • Leena Patel

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. © 2012 The Auther.

Bibliographical metadata

Original languageEnglish
Pages (from-to)867-877
Number of pages10
JournalAmerican Journal of Epidemiology
Volume175
Issue number9
DOIs
Publication statusPublished - 1 May 2012