The Presence of the d3-Growth Hormone Receptor Polymorphism Is Negatively Associated with Fetal Growth but Positively Associated with Postnatal Growth in Healthy Subjects

Context: A common polymorphism in the GH receptor (GHR) gene has been linked to increased growth response in GH-treated patients. No former study has focused on the association to prenatal growth. Objective: The aim of the study was to evaluate the association between the d3-GHR isoforms and spontaneous pre- and postnatal growth. Design: A prospective study was conducted on third-trimester fetal growth velocity (FGV), birth weight, birth length, and postnatal growth. Setting: The study was conducted at Copenhagen University Hospital. Participants: A total of 115 healthy adolescents were divided into those born small for gestational age (SGA) and appropriate for gestational age with or without intrauterine growth restriction. Main Outcome Measures: FGV was measured by serial ultrasonography, birth weight, birth length, and adolescent height. Isoforms of the d3-GHR gene (fl/fl, d3/fl, and d3/d3) were determined. Results: The prevalence of the d3-GHR isoforms was 50% but differed among the groups (P = 0.006), with a high prevalence (88%) in the group born SGA with verified intrauterine growth restriction. The d3-GRH allele were associated with decreased third-trimester FGV (P = 0.05) in SGA subjects. In the entire cohort, carriers of the d3-GHR allele had a significantly increased height (−0.10 vs. 0.34 sd score; P = 0.017) and change in height from birth to adolescence compared with carriers of the full-length GHR allele (0.57 vs. −0.02 sd score; P = 0.005). Conclusions: This study showed an increased spontaneous postnatal growth velocity in the carriers of the d3-GHR allele. Interestingly, we found the opposite effect on prenatal growth in the SGA group, with a decreased FGV in carriers of the d3-GHR allele.