Sodium coupled Neutral Aminoacid Transporter 2 (SNAT2) Intron1 methylation levels and Single Nucleotide Polymorphism in IUGR placentas

A reduction in placental nutrient transport is clearly involved in Intrauterine Growth Restriction (IUGR). The Sodium coupled Neutral Aminoacid Transporter 2 (SNAT2) has a crucial role in the control of fetal growth, promoting the transport of neutral aminoacids from the mother to the fetus. We recently demonstrated that SNAT2 mRNA expression is significantly lower in human IUGR compared to control placentas. The SNAT2 Intron1 (Int1) is an important regulatory region: it activates SNAT2 expression in aa deficiency conditions; Int1 presents many CpG islands. We measured its methylation levels in IUGR vs control placentas and we investigated a possible association with IUGR of a Single Nucleotide Polymorphism (SNP) located in the Int1, in which the ancestral nucleotide is a Cytosine belonging to a CpG island. Methylation levels of 13 CpG islands located in the SNAT2 Int1 were analysed by Pyrosequencing in 37 IUGR and 28 control placentas, and in 10 peripheral blood from healthy adults as external control. We genotyped the Int1 SNP in 68 IUGR and 34 control placentas. No significant differences were found in methylation levels between IUGR and controls. Interestingly, methylation was steadily low in all the observed CpGs. No association was found between the Int1 SNP and IUGR, analysing data under a codominant, a dominant and a recessive model. Hypomethylation of control samples (placenta and healthy adults) confirm the great importance of SNAT2, since it is known that CpG islands hypomethylation is a guarantee for gene expression, giving to the gene the potential of being expressed. Our results suggest that the alteration of SNAT2 mRNA that we found in IUGR compared to control placentas, is not due to epigenetic modifications in the SNAT2 Int1 and that IUGR is not associated to the SNP located in this region.