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GH deficiency status combined with GH receptor polymorphism affects response to GH in children.

Farmer, Pierre, Valsesia, Armand, Chatelain, Pierre and Clayton, Peter (2015) GH deficiency status combined with GH receptor polymorphism affects response to GH in children. European Journal of Endocrinology, 173 (6). pp. 777-789. ISSN 1479-683X


Meta-analysis has shown a modest improvement in first-year growth response to recombinant human GH (r-hGH) for carriers of the exon 3-deleted GH receptor (GHRd3) polymorphism but with significant interstudy variability.
The associations between GHRd3 and growth response to r-hGH over 3 years in relation to severity of GH deficiency (GHD) were investigated in patients from 14 countries. Treatment-naı¨ve pre-pubertal children with GHD were enrolled from the PREDICT studies (NCT00256126 and NCT00699855), categorized by peak GH level (peak GH) during provocation test: %4 mg/l (severe GHD; nZ45) andO4 to!10 mg/l mild GHD; nZ49) and genotyped for the GHRd3 polymorphism (full length (fl/fl, fl/d3, d3/d3). Gene expression (GE) profiles were characterized at baseline. Changes in growth (height (cm) and SDS) over 3 years were measured. There was a dichotomous influence of GHRd3 polymorphism on response to r-hGH, dependent on peak GH level. GH peak level (higher vs lower) and GHRd3 (fl/fl vs d3 carriers) combined status was associated with height change over 3 years (P!0.05). GHRd3 carriers with lower peak GH had lower growth than subjects with fl/fl
(median difference after 3 years K3.3 cm; K0.3 SDS). Conversely, GHRd3 carriers with higher peak GH had better growth (C2.7 cm; C0.2 SDS). Similar patterns were observed for GH-dependent biomarkers. GE profiles were significantly different between the groups, indicating that the interaction between GH status and GHRd3 carriage can be identified at a transcriptomic level. This study demonstrates that responses to r-hGH depend on the interaction between GHD severity
and GHRd3 carriage.

Item Type: Article
Keywords: GH deficiency, GH receptor polymorphism, GHRd3, pharmacogenomics
Date Deposited: 13 Jun 2016 23:45
Last Modified: 13 Jun 2016 23:45


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