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.