Pharmacogenomics of GH-Induced Catch-Up Growth in Prepubertal Short Children. The Role of the Exon 3-Deleted/Full-Length Growth Hormone Receptor Polymorphism

  • Antonio Carrascosa
  • Laura Audí


Differences in GH therapy-induced catch-up growth according to the exon 3-deleted/full-length-GHR genotype carried were first described in 2004 in children with idiopathic short stature (ISS) and in children born small for gestational age (SGA): children with d3/d3 and d3/fl genotypes grew more than those with the fl/fl genotype. However, recent studies failed to confirm these results. Here we summarize our data together with those reported by others on the influence of exon 3-deleted/full-length-GHR genotypes on (1) adult height reached by populations with normal growth, (2) spontaneous growth rate in preterm children, and (3) spontaneous growth rate and GH-induced catch-up growth in short prepubertal SGA, ISS, and growth hormone-deficient (GHD) children. Adult height in populations with normal growth: The exon 3-deleted/full-length-GHR genotype distribution does not influence adult height (n = 1,116); however, a tendency toward taller adult height was observed in subjects with the d3/d3 genotype. Spontaneous growth rate: While exon 3-deleted/full-length-GHR genotypes might play a role in spontaneous catch-up growth during the early years of life in preterm infants (n = 77), they do not clinically influence the prepubertal growth rate in short SGA, ISS, and GHD patients (n = 985). Catch-up growth induced by GH therapy in prepubertal short SGA, ISS, and GHD patients: To date, GH therapy-induced catch-up growth according to the three exon 3-deleted/full-length-GHR genotypes has been evaluated in 1,166 short SGA, ISS, or GHD children treated with varying GH doses for 1 or 3 years. Despite differences in clinical conditions (SGA, ISS, and GHD), GH dosage (30–66 μg/kg/day), and duration of GH therapy, clinically significant differences in catch-up growth induced by GH therapy were only observed in 172 (13.8%) of the 1,166 patients evaluated (d3/d3, n = 24; d3/fl, n = 62; and fl/fl, n = 86), while no clinically significant differences were found in the remaining 994 (86.2%) patients (d3/d3, n = 117; d3/fl, n = 363; and fl/fl, n = 514). In summary, adult height in normal populations, spontaneous prepubertal growth in short SGA, ISS, and GH-deficient children, and the catch-up growth induced by GH therapy in SGA, ISS, and GHD patients do not appear to be influenced by exon 3-deleted/full-length-GHR genotypes, while spontaneous catch-up growth in preterm infants could be.


Growth Hormone Growth Hormone Deficient Adult Height Growth Hormone Response Growth Hormone Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Exon 3-deleted/full-length-GHR genotypes


Growth hormone


Growth hormone deficiency


Growth hormone receptor


Insulin-like growth factor 1


Idiopathic short stature


Small for gestational age



M. Fernández-Cancio, C. Esteban, P. Andaluz, E. Vilaró, M. Clemente, D. Yeste, MA Albisu, and M. Gussinyé are acknowledged for their contribution to the Spanish studies. Christine O'Hara is acknowledged for useful help with the English version of the manuscript. This work was supported by grants from Institute of Health Carlos III, RCMN (C03/08), FIS PI-020803, and FIS PI-070145 from Ministerio de Ciencia y Tecnologia, Madrid, Spain.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Pediatric Endocrinology Unit, Department of Pediatrics, Institut de Rercerca Biomédica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) ISC IIIHospital Universitario Vall d’Hebron, Universidad Autónoma de BarcelonaBarcelonaSpain

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