miR-27a and miR-449b polymorphisms associated with a risk of idiopathic recurrent pregnancy loss

PLoS One. 2017 May 10;12(5):e0177160. doi: 10.1371/journal.pone.0177160. eCollection 2017.

Abstract

Objective: MicroRNAs (miRNAs) regulate gene expression during the peri-implantation period. The purpose of this study was to investigate whether genetic polymorphisms in the four miRNAs associated with fetal or placental development play roles in the development of idiopathic recurrent pregnancy loss (RPL) in Korean females.

Study design: A case-control study involving 225 controls and 387 women with at least two consecutively recurrent pregnancy losses between 1999 and 2012 was performed. The genotypes of the four miRNA polymorphisms, including miR-27a rs895819, miR-423 rs6505162, miR-449b rs10061133, and miR-605 rs2043556, were analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals were estimated using multivariate analyses after maternal age adjustments. The relationships between each of the four microRNA genotypes and each of the six clinical parameters of the RPL patients (plasma homocysteine and folate levels, natural killer cell number, platelet count, prothrombin time, and, activated partial thromboplastin time) were analyzed using multiple linear regression analyses.

Results: Our results suggest that weak associations between decreased RPL risk and the genotypes of miR-27a (AG and AG+GG), combination genotype of miR-27a/miR-423 (AG/GC), and haplotypes of miR-27a/miR-423/miR-449b/miR-605 (G-C-A-G) and miR-27a/miR-449b/miR-605 (G-A-G), whereas weak associations between increased RPL risk and genotypes of miR-449b (GG and AG+GG), combination genotypes of miR-423/miR-449b (CC/GG and CA/AG), miR-449b/miR-605 (AG/AG), haplotypes of miR-27a/miR-423/miR-449b/miR-605 (A-C-G-A, A-A-A-G, and G-C-G-G), miR-27a/miR-423/miR-449b (A-C-G), miR-27a/miR-449b/miR-605 (A-A-G, A-G-A, and G-G-G), miR-423/miR-449b/miR-605 (C-G-G and A-A-G), and miR-423/miR-449b (C-G and A-A). The genotypes of miR-27a (AG and AG+GG) also showed significant contributions to the prediction of folate levels in RPL patients.

Conclusions: The study showed associations between miRNA polymorphisms (miR-27a rs895819 and miR-449b rs10061133) and RPL development, and between the miRNA polymorphism (miR-27a rs895819) and plasma folate levels.

MeSH terms

  • Abortion, Habitual / blood
  • Abortion, Habitual / epidemiology
  • Abortion, Habitual / genetics*
  • Adult
  • Asian People / genetics
  • Blood Coagulation
  • Case-Control Studies
  • Cholesterol / blood
  • Female
  • Folic Acid / blood
  • Genotype
  • Humans
  • MicroRNAs / genetics*
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Republic of Korea / epidemiology
  • Risk Factors
  • Uric Acid / blood

Substances

  • MIRN27 microRNA, human
  • MIRN423 microRNA, human
  • MIRN449 microRNA, human
  • MIRN605 microRNA, human
  • MicroRNAs
  • Uric Acid
  • Folic Acid
  • Cholesterol

Grants and funding

This research was partly supported by Basic Science Research Programs through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (grants 2013R1A1A2009661, 2009-0093821 and 2015R1D1A1A09057432). This study was also partly supported by a grant of the Korea Healthcare technology R&D Project (HI15C1972010015), Ministry for Health, Welfare & Family Affairs, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.