The Effect of B₉ and B₁₂ Vitamins Deficiency on Hypomethylation of MMP-9 gene Promoter Among Women With Preterm Parturition

Preterm birth is one of the problems that pregnant women may encounter during pregnancy. Over-expression of Matrix metalloproteinases (MMPs) has the main role in the untimely remodeling of the extracellular matrix (ECM) and preterm delivery, but its exact mechanism is unknown. This study was undertaken to examine the methylation and expression patterns of this gene in women delivering preterm and also to analyze the correlation of serum B9 and B12 vitamins levels with expression and methylation of MMP-9 gene. The MMP-9 RNA and protein levels in 50 women delivering preterm and 50 women delivering at term were determined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA) methods. Methylation pattern of this gene was evaluated by Epitect Methyl-II PCR assay and methylation-sensitive restriction enzymes combined with PCR amplification method; then, their correlation with serum B₉ and B₁₂ vitamins was studied. Placental MMP-9 RNA and protein levels were higher (P < 0.03, P < 0.01) in women delivering preterm as compared to those delivering at term. We also observed significant hypomethylation of promoter of this gene in preterm samples (P < 0.012). Moreover, significant negative correlation between B₉ and B₁₂ vitamins concentration and hypomethylation of MMP-9 gene was seen (r = - 0.68 P < 0.001). Our study suggests an impressive role of deficiency of B9 and B12 vitamins concentration on the hypomethylation and overexpression of MMP-9 gene which may lead to preterm parturition of pregnant women.