IGF-II expression and methylation in small for gestational age infants

Background: Low birth weight is associated with an increased risk of adverse outcomes in many diseases in adult life. We investigated the expression of IGF-II and the status of differentially methylated regions (DMR) in small for gestational age (SGA) infants after birth. Methods: Plasma IGF-II, IGF-II receptor (IGF2R), IGF-I, and IGF-binding protein 3 (IGFBP3) levels were measured after birth in 150 newborn infants. These included 30 term appropriate for gestational age (AGA), 30 term SGA, 30 term large for gestational age (LGA), 30 preterm AGA, and 30 preterm SGA infants. H19 and IGF2 mRNA levels were quantified by fluorescence quantitative polymerase chain reaction (PCR). The methylation status of H19 DMR and IGF2 DMR2 was assessed by methylation-specific PCR (MSP). Plasma IGF-II, IGF2R, IGF-I, and IGFBP3 levels were measured by enzyme-linked immunosorbent assay in AGA infants of different gestational ages and term AGA infants on different days. Result: Plasma IGF-II levels after birth were lower in both term SGA (435.1 +/- 33.82 vs. 620.4 +/- 44.79, p=0.002) and LGA infants (483.7 +/- 33.8 vs. 620.42 +/- 44.79, p=0.018) than in term AGA infants. The expression of IGF2 mRNA was higher in the term SGA group than in the preterm SGA group (p=0.014) and the preterm SGA group displayed lower expression than the preterm AGA group (p=0.048). The H19 DMR methylation level was higher in both term SGA (p=0.044) and term LGA infants (p=0.027) compared to term AGA infants. Conclusions: IGF-II was associated with birth weight and expressed at high levels, which suggests that IGF-II may continue to play an important role after birth. H19 DMR methylation may be involved in controlling IGF-II expression.