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Context: The exon-3 deleted GH receptor (GHRd3) 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 GHRd3 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 GHRd3 on growth parameters were included. Principal outcomes were baseline height sd score (SDS) and the weighted average of change in growth velocity (Δ cm/yr) and height gain (Δ 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 GHRd3 compared with GHRwt-wt. In GHRd3, 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 GHRwt-wt. Meta-regression demonstrated a larger difference between GHRd3 and GHRwt-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 GHRd3 is associated with increased baseline height in GHD, but not in non-GHD. Furthermore, GHRd3 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.

GHRd3 stimulates growth velocity by an additional effect of ∼0.5 cm during the first year of rhGH treatment.

Copyright © 2009 by The Endocrine Society
Issue Section:
Endocrine Care
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