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

University Departments of Growth and Reproduction (R.B.J., H.L., A.J.), and Neonatology (S.V., G.G.), Rigshospitalet, DK-2100 Copenhagen, Denmark; and Department of Gynaecology and Obstetrics (T.L.), Holbaek Sygehus, Sygehus Vestsjaelland DK-4300, Denmark

Address all correspondence and requests for reprints to: Rikke Beck Jensen, M.D., University Department of Growth and Reproduction, Rigshospitalet, Section 5064, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: rikke.beck{at}rh.hosp.dk.

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.

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