The growth hormone receptor exon 3-deleted/full-length polymorphism and response to growth hormone therapy in prepubertal idiopathic short children.
OBJECTIVE
The primary aim of the study was to evaluate d3-GHR as a possible cause of increased GH sensitivity in children with delayed infancy-childhood transition (DICT). The secondary aim was to investigate the impact of the GHR exon 3 deleted/full-length (d3/fl) polymorphism on GH treatment response in prepubertal children classified as having idiopathic short stature (ISS).


METHODS
Study subjects included 167 prepubescent longitudinally followed children classified as having ISS. Children were randomized to standard-dose GH treatment (33 μg kg(-1) day(-1)), to double-dose treatment (67 μg kg(-1) day(-1)), or to an untreated control group. Growth and metabolic outcome were evaluated at birth (n = 166), after one year of treatment (n = 59) and at adult height (n = 145). Genotyping of the GHR d3/fl polymorphism was performed using TaqMan SNP genotyping of tagSNP rs6873545.


RESULTS
Birth and early growth data did not reach the predetermined level of statistical significance for difference between genotypes. Growth and IGF-1 response after one year of GH treatment did not differ between genotypes. IGFBP-3SDS was higher in untreated d3-GHR carriers than in untreated fl/fl individuals, whereas there was insufficient evidence for higher IGFBP-3SDS in treated d3-GHR carriers. Genotype did not explain the growth response to treatment, and no differences in heightSDS, height gain, or difference in height to midparental heightSDS between genotype groups were found at adult height.


CONCLUSIONS
The common GHR d3/fl polymorphism is probably not a cause of DICT in children with ISS, and our results do not suggest that the d3-GHR genotype is associated with increased sensitivity to GH in children with ISS.
Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: gunnel.hellgren@gu.se.
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G
Hellgren
Department of Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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CA
Glad
Department of Women and Child Health, Uppsala University, Uppsala, Sweden.
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B
Jonsson
Department of Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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G
Johannsson
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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Albertsson-Wikland
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006130:Growth Disorders / Q000188:drug therapy* / Q000235:genetics*; D013006:Growth Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011627:Puberty / Q000235:genetics; D055815:Young Adult
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D013006:Growth Hormone
Exon 3 deletion; Growth hormone receptor; Growth hormone treatment; Idiopathic short stature; Prepubertal children