The presence of the d3-growth hormone receptor polymorphism is negatively associated with fetal growth but positively associated with postnatal growth in healthy subjects

J Clin Endocrinol Metab. 2007 Jul;92(7):2758-63. doi: 10.1210/jc.2007-0176. Epub 2007 Apr 10.

Abstract

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.

MeSH terms

  • Adolescent
  • Adolescent Development / physiology*
  • Birth Weight / genetics
  • Cohort Studies
  • Female
  • Fetal Development / genetics*
  • Gestational Age
  • Heterozygote
  • Homozygote
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / growth & development
  • Infant, Small for Gestational Age / physiology
  • Male
  • Polymorphism, Genetic
  • Pregnancy
  • Prevalence
  • Prospective Studies
  • Receptors, Somatotropin / genetics*

Substances

  • Receptors, Somatotropin