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Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women

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Abstract

Background

The folate metabolism that converts homocysteine to methionine is closely related to the accumulation of homocysteine. Increased homocysteine levels lead to an impaired antithrombotic function of the vascular endothelium and uterine-placental circulation, resulting in abnormal pregnancy outcomes. Previous studies have reported that gene polymorphisms in folate metabolism are associated with the development of preterm birth (PTB) in various populations.

Objective

we performed a case–control study to evaluate the association between five polymorphisms in folate metabolic genes (MTHFR, MTR, MTRR, TCN2) and PTB.

Methods

In this study, a total of 254 subjects were analyzed (111 patients with PTB and 143 women at ≥ 38 weeks of gestation). Genotype and allele frequency differences between patients and control groups and the Hardy–Weinberg equilibrium were assessed using a Chi-square test. For evaluation indicators, odds ratios (ORs) of 95% confidence intervals (CI) were estimated. In addition, we analyzed the combined genotype frequencies of SNPs of folate-metabolizing genes to measure gene–gene interactions for PTB.

Results

Our results showed that the MTR rs1805087 GG (p = 0.031), and TCN2 rs1801198 CG genotype (OR 0.53, 95% CI 0.288–0.980, p = 0.042) were significantly associated with PTB. The MTHFR rs4846049 AA showed a marginal trend toward significance (OR 0.15, 95% CI 0.018–1.205, p = 0.041). In particular, the combined genotypes, including MTHFR rs1537514 CC—MTRR rs1801394 GG, MTHFR rs1537514 CC—TCN2 rs1801198 CG, and MTR rs1805087 AA—TCN2 rs1801198 CG, have significant interactions with PTB (OR 0.49, 95% CI 0.248–0.992, p < 0.05).

Conclusion

The polymorphisms of folate metabolic genes may have a genetic association with the development of PTB in Korean women. A larger sample set and functional studies are required to further elucidate our findings.

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Acknowledgements

We are grateful to all volunteers for providing DNA samples.

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Authors and Affiliations

  1. Department of Biological Sciences, College of Natural Science, Dankook University, Cheonan, Korea

    Bit Na Kwon, Noo Ri Lee, Hyung Jun Kim & Han Jun Jin

  2. Department of Obstetrics and Gynecology, Dankook University Hospital, Cheonan, Korea

    Yun Dan Kang, Jong Soo Kim & Jin Wan Park

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  1. Bit Na Kwon
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  2. Noo Ri Lee
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Correspondence to Han Jun Jin.

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Conflict of interest

Bit Na Kwon, Noo Ri Lee, Hyung Jun Kim, Yun Dan Kang, Jong Soo Kim, Jin Wan Park, Han Jun Jin declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the Dankook University. Informed consent was obtained from all individual participants included in the study.

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Kwon, B.N., Lee, N.R., Kim, H.J. et al. Folate metabolizing gene polymorphisms and genetic vulnerability to preterm birth in Korean women. Genes Genom 43, 937–945 (2021). https://doi.org/10.1007/s13258-021-01082-3

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