Growth Hormone Receptor Polymorphism and Growth Hormone Therapy Response in Children: A Bayesian Meta-Analysis

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 perf...

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Veröffentlicht in:American journal of epidemiology 2012-05, Vol.175 (9), p.867-877
Hauptverfasser: RENEHAN, Andrew G, SOLOMON, Mattea, CARRASCOSA, Antonio, HOKKEN-KOELEGA, Anita, JORGE, Alexander, MULLIS, Primus E, TAUBER, Maïthé, PATEL, Leena, CLAYTON, Peter E, ZWAHLEN, Marcel, MORJARIA, Reena, WHATMORE, Andrew, AUDI, Laura, BINDER, Gerhard, BLUM, Werner, BOUGNERES, Pierre, SANTOS, Christine Dos
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Sprache:eng
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Zusammenfassung: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.
ISSN:0002-9262
1476-6256
DOI:10.1093/aje/kwr408