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.

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American Journal of Epidemiology
Department of Pediatrics

Renehan, A., Solomon, M., Zwahlen, M., Morjaria, R., Whatmore, A., Audí, L., … Clayton, P. (2012). Growth hormone receptor polymorphism and growth hormone therapy response in children: A bayesian meta-analysis. American Journal of Epidemiology (Vol. 175, pp. 867–877). doi:10.1093/aje/kwr408