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The Effect of B9 and B12 Vitamins Deficiency on Hypomethylation of MMP-9 gene Promoter Among Women With Preterm Parturition

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Abstract

Preterm birth is one of the problems that pregnant women may encounter during pregnancy. Over-expression of Matrix metalloproteinases (MMPs) has the main role in the untimely remodeling of the extracellular matrix (ECM) and preterm delivery, but its exact mechanism is unknown. This study was undertaken to examine the methylation and expression patterns of this gene in women delivering preterm and also to analyze the correlation of serum B9 and B12 vitamins levels with expression and methylation of MMP-9 gene. The MMP-9 RNA and protein levels in 50 women delivering preterm and 50 women delivering at term were determined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA) methods. Methylation pattern of this gene was evaluated by Epitect Methyl-II PCR assay and methylation-sensitive restriction enzymes combined with PCR amplification method; then, their correlation with serum B9 and B12 vitamins was studied. Placental MMP-9 RNA and protein levels were higher (P < 0.03, P < 0.01) in women delivering preterm as compared to those delivering at term. We also observed significant hypomethylation of promoter of this gene in preterm samples (P < 0.012). Moreover, significant negative correlation between B9 and B12 vitamins concentration and hypomethylation of MMP-9 gene was seen (r =  − 0.68 P < 0.001). Our study suggests an impressive role of deficiency of B9 and B12 vitamins concentration on the hypomethylation and overexpression of MMP-9 gene which may lead to preterm parturition of pregnant women.

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Acknowledgements

We appreciate all of the participants in the study. We also thank Cellular and Molecular Research Center of Qazvin University of Medical Science for providing laboratory facilities.

Funding

This research was supported by a grant from cellular and molecular research center of Qazvin University of Medical Sciences.

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Authors and Affiliations

  1. Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, P.O. Box: 341197-5981, Qazvin, Iran

    Moeini N & Moghbelinejad S

  2. Faculty of Science, Department of Genetic, Islamic Azad University, Qom branch, Qom, Iran

    Moeini N

  3. Khatam Medical Genetic Lab, Qazvin, Iran

    Momeni AM & Moghbelinejad S

  4. Faculty of Science, Department of Microbiology, Islamic Azad University, Qom branch, Qom, Iran

    Zargar M

  5. Department of Obstetrics and Gynecology, School of Medicine, Qazvin University of Medical Science, Qazvin, Iran

    Abotorabi Sh & Habibi Nozari F

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  1. Moeini N
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  2. Momeni AM
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  3. Zargar M
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  4. Abotorabi Sh
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  5. Habibi Nozari F
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  6. Moghbelinejad S
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Contributions

We confirm the coauthors participated in the authorship as follows: MN participated in data collection, data analysis, and wrote the first draft of the paper, MAM performed laboratory tests, ZM has supervised the genetic assays, AS has assisted in data collection, HF has assisted in sampling, and MS involved in the conception, designing, supervising the project, and revising the manuscript draft.

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Correspondence to Moghbelinejad S.

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N, M., AM, M., M, Z. et al. The Effect of B9 and B12 Vitamins Deficiency on Hypomethylation of MMP-9 gene Promoter Among Women With Preterm Parturition. Biochem Genet 60, 336–350 (2022). https://doi.org/10.1007/s10528-021-10099-y

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  • DOI: https://doi.org/10.1007/s10528-021-10099-y

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