TY - JOUR
T1 - Growth hormone receptor polymorphism and growth hormone therapy response in children: A bayesian meta-analysis
AU - Renehan, Andrew G.
AU - Solomon, Mattea
AU - Zwahlen, Marcel
AU - Morjaria, Reena
AU - Whatmore, Andrew
AU - Audí, Laura
AU - Binder, Gerhard
AU - Blum, Werner
AU - Bougnres, Pierre
AU - Santos, Christine Dos
AU - Carrascosa, Antonio
AU - Hokken-Koelega, Anita
AU - Jorge, Alexander
AU - Mullis, Primus E.
AU - Tauber, Maïthé
AU - Patel, Leena
AU - Clayton, Peter E.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
KW - Bayesian meta-analysis
KW - genetic model
KW - growth hormone
KW - growth hormone receptor polymorphism
U2 - 10.1093/aje/kwr408
DO - 10.1093/aje/kwr408
M3 - Review article
SN - 0002-9262
VL - 175
SP - 867
EP - 877
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
IS - 9
ER -