Exon 3-deleted genotype of growth hormone receptor (GHRd3) positively influences IGF-1 increase at generation test in children with idiopathic short stature.
BACKGROUND
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).


METHODS
A total of 45 prepubertal ISS children were submitted to IGF-1 and IGFBP-3 generation test (4 days of hGH 33 microg/kg/day). Children were genotyped for GHR-exon 3: full-length (fl) and exon 3-deleted (d3) alleles.


METHODS
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 >or= 15 microg/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.


CONCLUSIONS
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.
Toyoshima
Marcos T K
MT
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Brazil.
Castroneves
Luciana A
LA
Costalonga
Everlayny F
EF
Mendonca
Berenice B
BB
Arnhold
Ivo J P
IJ
Jorge
Alexander A L
AA
D000367:Age Factors; D001827:Body Height; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D005091:Exons / Q000235:genetics*; D005260:Female; D005838:Genotype; D006128:Growth; D006130:Growth Disorders / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D019382:Human Growth Hormone; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010290:Parents; D011986:Receptors, Somatotropin / Q000235:genetics*; D012044:Regression Analysis; D017384:Sequence Deletion
D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I