- 作者：Peter Rzehak ; Veit Grote ; Eva Lattka ; Martina Weber ; Dariusz Gruszfeld ; Piotr Socha ; Ricardo Closa-Monasterolo ; Joaqu¨ªn Escribano ; Marcello Giovannini ; Elvira Verduci ; Philippe Goyens ; Fran?oise Martin ; Jean-Paul Langhendries ; Hans Demmelmair ; Norman Klopp ; Thomas Illig ; Berthold Koletzko
- 关键词：IGF-1 gene ; IGFBP-3 variants ; Protein formula ; IGF-I concentration ; Randomized clinical trial ; European Childhood Obesity Trial Study
- 刊名：Growth Hormone IGF Research
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：23
- 期：5
- 页码：149-158
- 全文大小：563 K
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.