Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk

Abstract

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.