Endocrine Abstracts (2006) 11 P553

Prevalence of the main GH receptor polymorphisms in GH deficient children and in the general population

M Filisetti2, P Mella1, A Pilotta2, L Costa2, I Sparapani2, S Zanola2, B Guaragni2, B Felappi2, E Prandi2 & F Buzi2


1Institute of Molecular Medicine “A. Nocivelli”, Brescia, Italy; 2Department of Paediatrics, University of Brescia, Brescia, Italy.


GH acts at the target cell through the GH receptor (GHR), stimulating a cascade of events that leads to target gene transcription. Polymorphisms of the GHR (GHRPs) have been reported in the general population and have been described in exons 3, 6 and 10, although their prevalence is not well defined. It is conceivable that GHRPs might affect the growth response to exogenous GH in children with short stature of different origin. To evaluate the prevalence of the different GHRPs in the general population and in GH deficient (GHD) children, we analysed the GHR gene sequence in 54 prepubertal GHD children (11 females) (mean age 7.8 years (S.D. 3.96); mean height (Ht) SDS –1.95 (S.D. 0.66) and in 50 non-GHD subjects with normal stature. Informed written consent was obtained by the study subjects as well as approval by the local Ethical Committee. GHR exons were amplified by PCR using pairs of intronic primers. The presence of single or multiple mismatches in the PCR products was revealed by DHPLC. For exons in which mismatches were found by DHPLC, direct sequencing was performed by automatic sequencer. We found a high frequency of GHRPs in normal subjects, and in particular: Exon 3 deletion (del-3) in 37 subjects (74%); Polymorphism 504 A>G at codon 168 of exon 6 (Poly6) in 44 subjects (88%); Polymorphism 1576 A>C at codon 526 of exon 10 (Poly10)in 33 subjects (66%). In most subjects these different polymorphisms recurred in association. In GHD subjects the polymorphism prevalence was slightly different: del-3 in 26 subjects (48%; P=0.01); Poly6 in 44 subjects (82%; NS); Poly10 in 35 subjects (65%; NS). In GHD patients too the different polymorphisms recurred in association. In conclusion, the main GHRPs show a similar prevalence in GHD subjects and in normal controls, except for del-3, that seems to be more frequent in the general population.

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