Association of biochemical parameters and RAGE gene polymorphisms in healthy infants and their mothers

• Published in: Clinica chimica acta Vol. 411; no. 15; pp. 1034 - 1040
• Main Authors: Boor, P., Celec, P., Klenovicsová, K., Vlková, B., Szemes, T., Minárik, G., Turňa, J., Šebeková, K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-08-2010
• Subjects: Adult; Advanced glycation end-products (AGEs); Ager SNP; Blood Glucose - metabolism; Diet; Female; Glycation End Products, Advanced - blood; Health; Humans; Infant; Infant Formula; Inflammation - blood; Inflammation - metabolism; Insulin resistance; Male; Milk, Human; Mothers; Nutrigenomics; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; sICAM-1; sRAGE; sICAM-1; Insulin resistance; Nutrigenomics; sRAGE; Ager SNP; Advanced glycation end-products (AGEs)
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2010.03.033

The receptor for advanced glycation end-products (RAGEs) and its gene polymorphisms are implicated in the pathogenesis of different chronic diseases including diabetes and its complications. Infant formulas contain high amounts of advanced glycation end-products (AGEs) — the ligands of RAGE.
In this cross-sectional study, we examined the impact of G82S and −374 A/T polymorphisms in the gene encoding RAGE on standard blood chemistry, soluble (s)RAGE and inflammatory markers in 244 healthy infants (3–16
months of age) and in 119 healthy mothers. Children were subdivided according to age (younger and older than 8
months) and for the −374 A/T polymorphism according to the feeding regimen (breast-fed vs. infant formula-fed).
Minor allele of the RAGE gene polymorphism G82S was associated with reduced plasma sRAGE in all age groups and with increased sICAM-1 in older children and mothers. Minor allele carrying mothers had decreased insulin sensitivity and HDL. The A allele of the RAGE gene promoter polymorphism −374 A/T was associated with higher indices of insulin resistance in young infant formula-fed, but not breast-fed children. In older, formerly infant formula-fed children signs of insulin resistance diminished, while formerly breast-fed children with A allele were more insulin sensitive.
The phenotype of minor allele carriers in G82S is associated with reduced levels of protective sRAGE in healthy infants. With increasing age sICAM-1 levels increased and insulin resistance developed. In early childhood the phenotype of the −374 A/T polymorphism was diet-dependently associated with changes in glucose metabolism, which diminished with increasing age.