Matrix metalloproteinases 1, 2, 3 and 9 functional single-nucleotide polymorphisms in idiopathic recurrent spontaneous abortion

Abstract

Idiopathic recurrent spontaneous abortion (IRSA) has been associated with abnormalities in the remodelling of endometrial extracellular matrix, as well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA women and chorionic villi of IRSA concepti. This study investigated the association of five functional MMP gene promoter polymorphisms (MMP1 −1607 1G/2G, MMP2 −735 C/T, MMP2 −1306 C/T, MMP3 −1612 5A/6A and MMP9 −1562 C/T) with IRSA. A total of 149 couples with at least three consecutive IRSA and 149 fertile couples were included in a case–control study. Genotype analysis was performed using PCR restriction fragment length polymorphism. Statistically significant differences were found in distributions of MMP2 −735 CT (chi-squared 10.21, P=0.006; OR 2.15, 95% CI 1.34–3.45, P=0.001), and MMP9 −1562 CC (chi-squared 9.06, P=0.010; OR 2.21, 95% CI 1.30–3.80, P=0.004) between IRSA women and controls. Combined analysis of MMP gene polymorphisms did not increase their predictive value. There were no statistically significant differences in genotype and allele frequencies of any polymorphism between IRSA men and controls. MMP2 −735 C/T and MMP9 −1562 C/T functional gene polymorphisms might be associated with an increased risk of IRSA in women.Considering the insufficient knowledge on genetic contribution to pregnancy loss, studies on genetic causes of idiopathic recurrent spontaneous abortion (IRSA) are of great importance. Development of a histologically and functionally normal endometrium is critical for subsequent endometrial decidualization, receptivity and implantation. The proper communication and interaction between maternal decidual cells and the embryo is essential for the establishment of a functional fetal–maternal interface. IRSA has been associated with abnormalities in the remodelling of endometrial extracellular matrix, as well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA women and chorionic villi of IRSA concepti. The aim of this study was to investigate the association of five functional MMP gene promoter polymorphisms with IRSA. A total of 149 couples with at least three consecutive IRSA and 149 fertile couples were included in a case–control study. Genotype analysis was performed using polymerase chain reaction and restriction fragment length polymorphism. Statistically significant differences were found in distribution of MMP2 −735 CT and MMP9 −1562 CC genotypes between IRSA and control women. Combined analysis of MMP gene polymorphisms did not increase their predictive value. There were no statistically significant differences in distribution of genotype and allele frequencies of any polymorphism between IRSA men and controls. Our results demonstrate that MMP2 −735 C/T and MMP9 −1562 C/T functional gene polymorphisms might be associated with an increased risk of IRSA in women.