Association Study between the Polymorphisms of Matrix Metalloproteinase (MMP) Genes and Idiopathic Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257–0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483–0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study

“…Despite various clinical and experimental tests, yet there is not an accurate and efficient diagnostic method during the early stages of pregnancy in more than half of RPL patients 3 . The risk factors linked to its pathogenesis are genetic disorders such as foetal chromosomal abnormalities, maternal factors including anatomical deformities, placental anomalies, thrombophilia, endocrine disorders, immune dysfunction, infection, smoking, psychological trauma, stress and environmental factors 4,5 . Among these factors, immune function appears to play a significant role in protecting the pregnancy by preventing response to the semi allograft 6 .…”

Matrix metalloproteinases 7, 8, 12, 13 gene haplotypes associated with colorectal cancer in a Mexican population

“…8 Thus, it could be that there is a stronger haplotypic force deriving from the presence of a specific allele and not from the sum of all alleles. On the other hand, in the haplotype analysis of three SNVs (MMP8 rs2509013 C>T/MMP8 rs11225395 G>A/MMP27 rs3809017 T>C), 22 most haplotypes that had T were associated with a decrease in the recurrence of pregnancies; therefore, the influence of a single allele could be relevant.…”

Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

“…Several gene polymorphisms affect the risk of RPL, such as matrix metalloproteinase genes [36], the methylenetetrahydrofolate reductase (MTHFR) gene [37], complement factors D and H [38], and genome wide methylation analysis [39], reflecting the complicated mechanisms that underlie the development of RPL. Previous studies have investigated the association of high levels of homocysteine and low levels of folate with the risk of RPL [40,41].…”