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Genes (Basel). 2019 May 7;10(5). pii: E347. doi: 10.3390/genes10050347.

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

Author information

1
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea. hahnsung@naver.com.
2
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea. fise123@naver.com.
3
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea. jokim8505@gmail.com.
4
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea. tody2209@naver.com.
5
Department of Obstetrics and Gynecology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea. happyiran@cha.ac.kr.
6
Fertility Center of CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea. bin0902@chamc.co.kr.
7
Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 06125, Korea. wooslee@cha.ac.kr.
8
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea. nkkim@cha.ac.kr.

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.

KEYWORDS:

MMP-27; MMP-8; matrix metalloproteinase (MMP); polymorphism; recurrent pregnancy loss (RPL)

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