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- Title
Exon 3-deleted genotype of growth hormone receptor ( GHRd3) positively influences IGF-1 increase at generation test in children with idiopathic short stature.
- Authors
Toyoshima, Marcos T. K.; Castroneves, Luciana A.; Costalonga, Everlayny F.; Mendonca, Berenice B.; Arnhold, Ivo J. P.; Jorge, Alexander A. L.
- Abstract
Context A GHR-exon 3 polymorphism has been reported to influence the growth response to hGH therapy in short stature children. None of these studies provided data on IGF-1 generation test. Objective To evaluate the influence of the GHR-exon 3 polymorphism on the generation test in children with idiopathic short stature (ISS). Design and patients A total of 45 prepubertal ISS children were submitted to IGF-1 and IGFBP-3 generation test (4 days of hGH 33 µg/kg/day). Children were genotyped for GHR-exon 3: full-length (fl) and exon 3-deleted (d3) alleles. Measurements IGF-1 and IGFBP-3 increment as absolute values and standard deviation scores (SDS). Results Basal clinical and laboratory data were similar among patients with different genotypes (fl/fl vs. fl/d3 or d3/d3). All patients presented IGF-1 increase ≥ 15 µg/l at generation test. Children with GHRd3 allele, as a group, presented a statistically significant higher IGF-1 SDS increase at generation test than children homozygous for GHRfl allele (1·0 ranging from 0·1 to 3·7 for fl/fl vs. 1·2 ranging from 0·3 to 4·4 for fl/d3 and d3/d3; P = 0·037). Multiple linear regression found a positive association between increase in IGF-1 SDS with chronological age ( P = 0·007) and GHR genotype ( P = 0·027), which together explain 24% of the variability of IGF-1 SDS increment at generation test. There was no difference in IGFBP-3 generation test between the two genotype groups. Conclusion This study demonstrates that ISS children carrying the GHRd3 allele, as a group, present a slightly higher GH sensitivity regarding short-term IGF-1 generation during hGH stimulus than children homozygous for GHRfl allele.
- Subjects
GENETIC polymorphisms; ANTHROPOMETRY; BODY size; SOMATOTROPIN; HORMONE receptors; STANDARD deviations; ANALYSIS of variance
- Publication
Clinical Endocrinology, 2007, Vol 67, Issue 4, p500
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/j.1365-2265.2007.02915.x