The Leu544Ile polymorphism of the growth hormone receptor gene affects the serum cholesterol levels during GH treatment in children with GH deficiency

Summary Objective The cellular effects of growth hormone (GH) are mediated by the interaction between GH and the GH receptor (GHR). We investigated the association between polymorphisms in GHR and changes in height standard deviation scores (SDS), and lipid metabolism during GH treatment for GH‐deficient children. Design A 1‐year study on growth rate and lipid metabolism under GH treatment. Patients Eighty‐three children (61 boys and 22 girls) with GH deficiency were treated with GH for 1 year after diagnosis. Intervention The patients were treated with recombinant human GH (0·19 mg/kg/week) for at least 1 year after diagnosis. The growth rates and biochemical parameters for lipid metabolism were measured both before and during treatment. Four single nucleotide polymorphisms (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3 deletion polymorphisms were genotyped by direct sequencing and multiplex PCR. Results We found no significant association between GHR polymorphisms and changes in height SDS during GH treatment. The total cholesterol levels of the GH‐deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol levels before GH treatment and then maintained high levels during the GH treatment, compared to those with other genotypes. No other polymorphisms seemed to have any apparent effects on lipid metabolism. Conclusion The Leu544Ile polymorphism of the GHR gene is associated with cholesterol levels in boys with GH deficiency.