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Rzehak, P.* ; Grote, V.* ; Lattka, E. ; Weber, M.* ; Gruszfeld, D.* ; Socha, P.* ; Closa-Monasterolo, R.* ; Escribano, J.* ; Giovannini, M.* ; Verduci, E.* ; Goyens, P.* ; Martin, F.* ; Langhendries, J.P.* ; Demmelmair, H.* ; Klopp, N. ; Illig, T. ; Koletzko, B.* ; European Childhood Obesity Trial Study Group (*)

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. 23, 149-158 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 1.6g/100mL) or higher (HP: 2.05 and 3.2g/100mL) protein contents for the first 12months 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 6months 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 ~1.3ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3ng/mL and ~1.3 and decreased in BF infants by ~0.6ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450ng/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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Igf-1 Gene ; Igfbp-3 Variants ; Protein Formula ; Igf-i Concentration ; Randomized Clinical Trial ; European Childhood Obesity Trial Study; Growth-factor-i ; Binding Protein-3 ; Cancer Risk ; Hormone Deficiency ; Follow-up ; Igfbp-3 ; Breast ; Polymorphisms ; Children ; Formula
ISSN (print) / ISBN 1096-6374
e-ISSN 1096-6374
Journal Growth Hormone and IGF Research
Quellenangaben Volume: 23, Issue: 5, Pages: 149-158 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)