Common exon 3 polymorphism of the GH receptor (GHR) gene and effect of GH therapy on growth in Korean children with idiopathic short stature (ISS).
OBJECTIVE
A human GH receptor (GHR) gene exon 3 polymorphism (d3-GHR) has been reported to be associated with responsiveness to GH therapy. We assessed the frequencies of this polymorphism in Korean control and idiopathic short stature (ISS) populations, and analysed short-term growth response to GH therapy according to GHR-exon 3 genotypes in Korean children with ISS.


METHODS
This was a retrospective study in 158 ISS children. Auxological and endocrine parameters were measured, and the GHR-exon 3 genotype was analysed. Allelic frequencies of GHR-exon 3 genotype were compared between the ISS group and a control group. GH had been administered for 62 patients, 52 of whom remained prepubertal after the first follow-up year. Changes in height velocity (HV) and IGF-1 and IGFBP-3 concentrations following GH therapy were compared in patients with these genotypes.


RESULTS
There was no difference in GHR-exon 3 genotype frequency between ISS and control groups of Koreans. However, the fl/fl genotype was more frequent in Koreans than in Caucasians. ISS children with d3-GHR showed a significantly higher increment in HV (P = 0.002) and a marginally significant increment in IGF-1 concentration (P = 0.064) at the first year of GH therapy.


CONCLUSIONS
fl-GHR was more frequently detected in a Korean population than in Caucasians. The growth promotion efficacy of GH therapy differed significantly between ISS patients with and without the d3-GHR allele. These findings indicate that the GHR-exon 3 polymorphism can affect the growth promoting efficacy of short-term GH therapy in Korean children with ISS.
Ko
Jung Min
JM
Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Park
Jung Young
JY
Yoo
Han-Wook
HW
D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000235:genetics*; D019382:Human Growth Hormone / Q000235:genetics* / Q000627:therapeutic use*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies
D002352:Carrier Proteins; D019382:Human Growth Hormone; C051815:somatotropin-binding protein