J Korean Med Sci.  2022 Nov;37(46):e336. 10.3346/jkms.2022.37.e336.

Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women

  • 1Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 2Bundang Cheil Women’s Hospital, Seongnam, Korea
  • 3Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
  • 4Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 5Seoul Clinical Laboratories Healthcare Co., Ltd., Yongin, Korea


Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls.
In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed.
The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/ miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/ AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively).
There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.


Plasma; MicroRNAs; Pregnancy; Recurrent Pregnancy Loss; Miscarriage


  • Fig. 1 Odds ratio of genotype combinations with significantly increased odds compared to reference. Odds ratio with 95% confidence interval in log scale.eNOS = endothelial nitric oxide synthase, TNF = tumor necrosis factor.


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