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Common Polymorphisms of the Growth Hormone (GH) Receptor Do Not Correlate with the Growth Response to Exogenous Recombinant Human GH in GH-Deficient Children

Department of Pediatrics (A.P., M.F., B.F., E.P., L.D.N., F.B.), Institute of Molecular Medicine A. Nocivelli (P.M.), and Section of Medical Statistics (G.P.), University of Brescia, 25123 Brescia, Italy

Address all correspondence and requests for reprints to: Dr. F. Buzi, Clinica Pediatrica dell’Università di Brescia, P.le Spedali Civili 1, 25123 Brescia, Italy. E-mail: fbuzi{at}med.unibs.it.

Context: GH acts through the GH receptor (GHR), whose polymorphisms might affect the growth response to recombinant human GH (rhGH).

Objective: The objective of this study was to investigate possible influences of GHR polymorphisms on the growth response to rhGH in GH-deficient (GHD) children.

Design: This was a 2-yr study (first year, spontaneous growth; second year, growth during rhGH treatment).

Setting: This study was performed at a referral center.

Patients: Fifty-four prepubertal GHD children (11 females; mean age, 7.8 yr; SD, 3.96) were studied.

Intervention: Patients were treated with rhGH (0.2 mg/kg·wk) for at least 1 yr after diagnosis. Growth velocity (GV) was measured 1 yr before treatment and during the first treatment year. 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 denaturing high-pressure liquid chromatography. For exons in which mismatches were found by denaturing high-pressure liquid chromatography, direct sequencing was performed by automatic sequencer.

Main Outcome Measures: Before the start of treatment, the mean height (Ht) SD score was –1.93 (SD, 0.70), and the mean GV SD score was –1.49 (SD, 1.26).

Results: The posttreatment (first 12 months) mean GV SD score was 3.55 (SD, 3.27). Molecular analysis revealed a high frequency of GHR polymorphisms; in particular: exon 3 deletion (Del 3) in 26 subjects (48%), polymorphism 504 A>G at codon 168 of exon 6 in 44 (82%), and polymorphism 1576 A>C at codon 526 of exon 10 in 35 (65%). In most patients, these different polymorphisms recurred in association. We found no significant differences in GV between the groups of subjects defined by the polymorphic genotypes.

Conclusion: The most common GHR polymorphisms, alone or in association, do not appear to affect the growth response to rhGH in GHD children.

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