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.

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.

Genetic variations in polyunsaturated fatty acid metabolism--implications for child health?

Sufficient nutritional supply with polyunsaturated fatty acids (PUFAs) has long been considered as beneficial for child health, especially in regard to neuronal development and allergic diseases. In recent years, genetic association studies showed that in addition to nutritional influences, the genetic background is highly important for PUFA composition in human tissues. Specifically, polymorphisms in the fatty acid desaturase genes or FADS determine the efficiency of how PUFAs are processed endogenously. Recent gene-nutrition interaction studies suggest that these polymorphisms modulate the effect of nutritional fatty acid intake on complex phenotypes such as cognitive outcomes and asthma risk in children. These early results may provide the basis for future well-specified dietary recommendations to achieve optimal health benefit for all children. This article presents results from recent gene-nutrition interaction studies, discusses its implications for child health, and gives an outlook how this association might translate into clinical practice in the future.