Homozygosity of the d3-growth hormone receptor polymorphism is associated with a high total effect of GH on growth and a low BMI in girls with Turner syndrome

Objective The protein polymorphism of the GH receptor caused by genomic deletion of exon 3 (d3) has been linked to the magnitude of the first-year-growth response to GH in girls with Turner syndrome. Here, we studied the long-term effect of GH therapy in Turner syndrome in correlation to this polymorphism. Design The study was mainly retrospective. Patients The women with Turner syndrome (n = 48) had been treated with GH over the past 18 years at our hospital. The mean GH dose used was 38 mu g/kg/day (SD 8). Measurements The GHR-exon 3 locus was genotyped using a PCR multiplex assay for both alleles and a second PCR assay for the full length (fl) allele only. Results The fl/fl, d3/fl and d3/d3 genotypes were present in 24, 17 and 7 women, respectively. Mean Turner height standard deviation scores (SDS) at start of therapy was 0.09 (1.09), mean age was 9.1 years (3). Age, height, target height, age at start of puberty and mode of GH therapy were not different between the groups. Total gain in height (difference between final adult height and initial height) was significantly higher in the d3/d3 group [+1.84 SDS (0.31)] than in the fl/fl group [+0.72 SDS (0.92)] and in the d3/fl group [+0.83 SDS (0.93)] (P < 0.001). A covariance analysis confirmed the effect of the polymorphism. Mean BMI SDS at the start and end of therapy was low in the d3/d3 group and significantly lower than in the fl/fl group (P < 0.04). Conclusions Our data suggest that homozygosity for the d3-GHR polymorphism is associated with a unique GH responsiveness and a weight regulation towards a lower BMI in girls with Turner syndrome.