Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial

Growth Horm IGF Res. 2013 Oct;23(5):149-58. doi: 10.1016/j.ghir.2013.05.002. Epub 2013 Jun 22.

Abstract

Objective: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied.

Design: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants.

Results: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing.

Conclusions: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.

Trial registration: ClinicalTrials.gov NCT00338689.

Keywords: European Childhood Obesity Trial Study; IGF-1 gene; IGF-I concentration; IGFBP-3 variants; Protein formula; Randomized clinical trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Breast Feeding
  • Eating / physiology*
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Humans
  • Infant
  • Infant Formula
  • Infant Nutritional Physiological Phenomena
  • Infant, Newborn / growth & development
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Milk Proteins / metabolism*
  • Polymorphism, Single Nucleotide*

Substances

  • Milk Proteins
  • Insulin-Like Growth Factor I

Associated data

  • ClinicalTrials.gov/NCT00338689