title: 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.affiliation: School of Cancer andEnabling Sciences, University of Manchester, United Kingdom. arenehan@picr.man.ac.uk
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Renehan
authors.forename: Mattea
authors.initials: M
authors.lastname: Solomon
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.forename: Reena
authors.initials: R
authors.lastname: Morjaria
authors.forename: Andrew
authors.initials: A
authors.lastname: Whatmore
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Werner
authors.initials: W
authors.lastname: Blum
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
authors.forename: Christine Dos
authors.initials: CD
authors.lastname: Santos
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.forename: Anita
authors.initials: A
authors.lastname: Hokken-Koelega
authors.forename: Alexander
authors.initials: A
authors.lastname: Jorge
authors.forename: Primus E
authors.initials: PE
authors.lastname: Mullis
authors.forename: Maïthé
authors.initials: M
authors.lastname: Tauber
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
mesh_terms: D001499:Bayes Theorem; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D018740:Genetic Heterogeneity; D006130:Growth Disorders / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D017594:Publication Bias
chemical_list: D002352:Carrier Proteins; D019382:Human Growth Hormone; C051815:somatotropin-binding protein