CONTEXT: The exon-3 deleted GH receptor (GHR(d3)) polymorphism is associated with an increased growth response to recombinant human GH (rhGH) therapy in some, but not all, studies in GH-deficient (GHD) and non-GHD children with short stature. OBJECTIVE: The aim of the study was to assess the effects of GHR(d3) on baseline height and the first year's growth response to rhGH treatment in prepubertal GHD and non-GHD children with short stature. DESIGN: We conducted a systematic review and meta-analysis. METHODS: Fifteen studies reporting the effect of GHR(d3) on growth parameters were included. Principal outcomes were baseline height sd score (SDS) and the weighted average of change in growth velocity (Delta cm/yr) and height gain (Delta height SDS) after 1 yr of rhGH. RESULTS: In GHD, not in non-GHD, baseline height SDS was 0.159 sd higher [95% confidence interval (CI), 0.020, 0.298] in GHR(d3) compared with GHR(wt-wt). In GHR(d3), rhGH therapy resulted in a higher increase in growth velocity (0.521 cm/yr; 95% CI, 0.196, 1.015) and height gain (0.075 sd; 95% CI, 0.007, 0.143) compared with GHR(wt-wt). Meta-regression demonstrated a larger difference between GHR(d3) and GHR(wt-wt) in studies using lower rhGH doses and carried out at a higher age, independently of the cause of short stature. CONCLUSIONS: This meta-analysis in prepubertal children with short stature indicates that GHR(d3) is associated with increased baseline height in GHD, but not in non-GHD. Furthermore, GHR(d3) stimulates growth velocity by an additional effect of approximately 0.5 cm during the first year of rhGH treatment, and this effect is more pronounced at lower doses of rhGH and higher age.
CONTEXT: The exon-3 deleted GH receptor (GHR(d3)) polymorphism is associated with an increased growth response to recombinant human GH (rhGH) therapy in some, but not all, studies in GH-deficient (GHD) and non-GHD children with short stature. OBJECTIVE: The aim of the study was to assess the effects of GHR(d3) on baseline height and the first year's growth response to rhGH treatment in prepubertal GHD and non-GHD children with short stature. DESIGN: We conducted a systematic review and meta-analysis. METHODS: Fifteen studies reporting the effect of GHR(d3) on growth parameters were included. Principal outcomes were baseline height sd score (SDS) and the weighted average of change in growth velocity (Delta cm/yr) and height gain (Delta height SDS) after 1 yr of rhGH. RESULTS: In GHD, not in non-GHD, baseline height SDS was 0.159 sd higher [95% confidence interval (CI), 0.020, 0.298] in GHR(d3) compared with GHR(wt-wt). In GHR(d3), rhGH therapy resulted in a higher increase in growth velocity (0.521 cm/yr; 95% CI, 0.196, 1.015) and height gain (0.075 sd; 95% CI, 0.007, 0.143) compared with GHR(wt-wt). Meta-regression demonstrated a larger difference between GHR(d3) and GHR(wt-wt) in studies using lower rhGH doses and carried out at a higher age, independently of the cause of short stature. CONCLUSIONS: This meta-analysis in prepubertal children with short stature indicates that GHR(d3) is associated with increased baseline height in GHD, but not in non-GHD. Furthermore, GHR(d3) stimulates growth velocity by an additional effect of approximately 0.5 cm during the first year of rhGH treatment, and this effect is more pronounced at lower doses of rhGH and higher age.
Authors: Samantha N Hartin; Waheeda A Hossain; Ann M Manzardo; Shaquanna Brown; Paula J Fite; Marco Bortolato; Merlin G Butler Journal: Growth Horm IGF Res Date: 2018-02-12 Impact factor: 2.372
Authors: Felipe Albuquerque Marques; Túlio Cesar Lins; Ricardo Moreno Lima; Rômulo Maia Carlos Fonseca; Nanci Maria de França; Ricardo Jacó de Oliveira; Maria Teresinha de Oliveira Cardoso; Rinaldo Wellerson Pereira; Robert Pogue Journal: Endocrine Date: 2013-06-28 Impact factor: 3.633