Influence of polymorphisms in genes encoding for insulin-like growth factor (IGF)-I, insulin, and IGF-binding protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 levels in umbilical cord plasma.

BACKGROUND/AIMS In postnatal life, polymorphisms in the promoter region of IGFBP3 were associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels. Whether these associations exist in utero has not been studied yet. Polymorphisms in the IGF1 promoter (polymorphic CA-repeat) and the insulin gene variable number tandem repeats locus (INS VNTR) are further polymorphisms of interest, because associations with birth weight have been reported. We aimed to investigate associations between polymorphisms in the promoter regions of IGF1 (wild type 192 bp), IGFBP3 (rs2854744; rs13241830), and INS VNTR (rs689) with cord plasma levels of IGF-I, IGF-II, and IGFBP-3. METHODS We measured IGF-I, IGF-II, and IGFBP-3 concentrations in cord blood from 677 neonates and genotyped the selected polymorphisms. RESULTS Carriers of the minor allele of both polymorphisms in the IGFBP3 gene had, on average, 4-5% lower IGFBP-3 levels per copy of the respective minor allele (p = 0.002 and p = 0.028) when compared to wild type carriers. The IGF1 promoter and the INS VNTR polymorphisms were not associated with IGF-I, IGF-II, or IGFBP-3 levels. CONCLUSIONS Our data show associations of cord plasma IGFBP-3 levels and the IGFBP3 gene variants but not of IGF1 promoter and INS VNTR polymorphisms with IGF-I, IGF-II, or IGFBP-3 levels in utero.