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

 Hye In Kim  ;  Eun A Choi  ;  Eun Chan Paik  ;  Soohyeon Park  ;  Yu Im Hwang  ;  Jae Hoon Lee  ;  Seok Kyo Seo  ;  SiHyun Cho  ;  Young Sik Choi  ;  Byung Seok Lee  ;  Jimyeong Park  ;  Sanghoo Lee  ;  Kyoung-Ryul Lee  ;  Bo Hyon Yun 
 JOURNAL OF KOREAN MEDICAL SCIENCE, Vol.37(46) : e336, 2022-11 
Journal Title
Issue Date
Abortion, Habitual* / diagnosis ; Abortion, Habitual* / genetics ; Biomarkers ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; MicroRNAs* / genetics ; Polymorphism, Single Nucleotide ; Pregnancy ; Republic of Korea ; Tumor Necrosis Factor-alpha / genetics
MicroRNAs ; Miscarriage ; Plasma ; Pregnancy ; Recurrent Pregnancy Loss
Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye In(김혜인) ORCID logo https://orcid.org/0000-0001-7961-5988
Seo, Seok Kyo(서석교) ORCID logo https://orcid.org/0000-0003-3404-0484
Yun, Bo Hyon(윤보현) ORCID logo https://orcid.org/0000-0001-5703-797X
Lee, Byung Seok(이병석) ORCID logo https://orcid.org/0000-0001-6001-2079
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0003-4223-1395
Cho, Si Hyun(조시현) ORCID logo https://orcid.org/0000-0003-2718-6645
Choi, Young Sik(최영식) ORCID logo https://orcid.org/0000-0002-1157-4822
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