ABSTRACT
OBJECTIVE: Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth. STUDY DESIGN: Amniotic fluid samples (14-18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR. RESULTS: Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P=0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P=0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P=0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR=0.289, 95%CI=0.1-0.9, P=0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups. CONCLUSIONS: High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.
Subject(s)
Amniotic Fluid/metabolism , Fetal Growth Retardation/metabolism , Infant, Small for Gestational Age , Insulin-Like Growth Factor Binding Proteins/metabolism , Pregnancy Trimester, Second/metabolism , Adult , Biomarkers/metabolism , Female , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Infant, Newborn , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Proteins/genetics , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Middle Aged , Minisatellite Repeats/genetics , Polymorphism, Genetic/genetics , Pregnancy , Risk FactorsABSTRACT
Poor embryo implantation can lead to poor feto-maternal exchanges and intrauterine growth restriction. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are highly involved in early embryo implantation and three functional polymorphisms have been described for these genes: MMP2 C-1306T, MMP9 C-1562T and MMP9 (CA)n repeat. We evaluated therefore the association between fetal genotype for these mutations and intrauterine growth retardation (IUGR). Amniotic fluid samples were obtained from 44 IUGR cases and 98 appropriate for gestational age (AGA) controls at 15-17 weeks gestation, and analyzed by PCR followed by restriction enzyme digestion or direct analysis on a Genetic Analyzer. Fetal MMP2 C-1306T mutation rate was higher within the IUGR than AGA population (P=0.001). The risk of IUGR occurrence was increased both in CT (OR=3.603; 95% CI=1.577-8.231; P=0.004) and TT carriers (OR=3.391; 95% CI=0.786-14.630; P=0.102), compared to the normal CC genotype. On the other side, fetal allele frequencies and genotype distributions for MMP9 C-1562T and MMP9 (CA)n were similar between the IUGR and AGA populations. We conclude that fetal MMP2 -1306 single nucleotide polymorphism (SNP) is associated with an increased risk for IUGR, but not MMP9 -1562 SNP nor MMP9 microsatellite.
