GH1 gene polymorphism in Polish children and adolescents with short stature - reanalysis based on diverse growth hormone secretion.

PURPOSE: The aim of this study was to reanalyze our previous results in terms of GH1 gene allele frequencies in children with short stature using a new approach with more diverse growth hormone (GH) peak level ranges along with an increased number of patients, and included height velocity analysis in the first year of recombinant human GH treatment. METHODS: The study group included 202 children with short stature, divided into three subgroups according to the serum GH peak level: <5 ng/ml; in the range between 5 and < 10 ng/ml; and ≥ 10 ng/ml. The control group included 180 children of normal height. PCR amplicons covering the whole coding sequence of the GH1 gene were sequenced by the Sanger method. RESULTS: Allele frequencies were established for all 13 studied SNPs. Only for one intronic SNP (rs41295245, G>A) frequencies differed significantly when compared patients with GH peak ≥ 10 ng/ml versus controls (P = 0.0224) and when compared patients with GH peak ≥ 10 ng/ml and patients with GH peak < 5 ng/ml (P = 0.0317). In a single patient, two additional missense variants were found. In exon 4 (11:g.63917914) the A>T substitution leads to p.Leu101His exchange, while in exon 5, the rs1423321088 A>G (p.Asp179Gly) was detected. CONCLUSION: Our study showed that intronic SNP in the GH1 gene may be associated with short stature despite normal GH serum concentrations. Two GH1 variants found in a single patient with low GH secretion could potentially affect structural properties of the protein, leading to short stature and GH deficiency.