Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.

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.

• Authors: Andrew G Renehan, Mattea Solomon, Marcel Zwahlen, Reena Morjaria, Andrew Whatmore, Laura Audí, Gerhard Binder, Werner Blum, Pierre Bougnères, Christine Dos Santos, Antonio Carrascosa, Anita Hokken-Koelega, Alexander Jorge, Primus E Mullis, Maïthé Tauber, Leena Patel, Peter E Clayton
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 175 Issue 9 Pg. 867-77 (May 01 2012) ISSN: 1476-6256 [Electronic] United States
• PMID: 22494952 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

• Carrier Proteins
• Human Growth Hormone
• somatotropin-binding protein

Topics

• Bayes Theorem
• Carrier Proteins (genetics)
• Child
• Genetic Heterogeneity
• Growth Disorders (drug therapy)
• Human Growth Hormone (therapeutic use)
• Humans
• Models, Genetic
• Polymorphism, Genetic
• Publication Bias