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.
Highlights
Pregnancy loss, referred to as spontaneous abortion, is defined as the loss of a clinical pregnancy prior to 20 weeks of gestational age
Given the weight of evidence implicating single nucleotide polymorphisms (SNPs) in Matrix metalloproteinases (MMPs) genes in the susceptibility to various medical conditions, we investigated the potential associations between Recurrent pregnancy loss (RPL) and polymorphisms of: (1) MMP-8, that have been found to be associated with spontaneous preterm delivery
Our results showed that MMP-8 rs2509013 C>T and MMP-27 rs3809017 T>C polymorphisms were significantly associated with decreased RPL susceptibility
Summary
Referred to as spontaneous abortion, is defined as the loss of a clinical pregnancy prior to 20 weeks of gestational age. Recurrent pregnancy loss (RPL) refers to consecutive pregnancy losses; the European Society for Human Reproduction and Embryology and the Royal College of Obstetricians and Gynecologists have defined RPL as the loss of three or more consecutive pregnancies. The American Society for Reproductive Medicine broadened the. RPL is a significant and distressing clinical concern, since 2–5% of couples that hope to have a baby experience RPL. Various etiological factors are reported to contribute to RPL, including thrombosis, advanced maternal age, maternal anatomic anomalies, chromosomal abnormalities, endocrine system dysfunction, antiphospholipid syndrome, immunological problems, uterine anomalies, hereditary thrombophilia, and environmental factors [2]. The underlying causes related to 30–40% of RPL cases are still unclear and several studies investigating the associations between potential genetic factors and RPL are currently underway
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