Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure

Abstract

One-carbon metabolism, in which folate plays an essential role, is important for maintaining pregnancy and foetal development. Here, polymorphisms in three genes involved in the methylation of homocysteine were examined: methionine synthase (MTR), methionine synthase reductase (MTRR), and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), each of which is involved in methionine metabolism, a component of the one-carbon metabolism process. This involved a case–control study of 343 Korean women: 118 patients with RIF and 225 controls with at least one live birth and no history of pregnancy loss. The MTHFD1 1958GA genotype was observed less frequently than the MTHFD1 1958GG genotype (IF ≥ 4, p = 0.015) in women with RIF. In addition, the MTRR 66A > G polymorphism was associated with increased plasma homocysteine levels (p = 0.019). Based on these results, we propose that the MTRR 66A > G and MTHFD1 1958G > A polymorphisms are predisposing factors for RIF development. This study is the first to examine a potential association between the MTHFD1 and MTRR polymorphisms and RIF susceptibility in Korean patients.

Keywords:

• One-carbon metabolism
• homocysteine
• polymorphism
• recurrent implantation failure

Acknowledgements

Nam Keun Kim designed and directed the whole project. Ji Hyang Kim, Young Ran Kim, and Woo Sik Lee collected the blood samples from RIF patients and control subjects. Sung Hwan Cho, Hui Jeong An, and Jung Oh Kim performed the experiments, collected the results, and analyzed the data. Sung Hwan Cho and Woo Sik Lee discussed and interpreted the data and results. Sung Hwan Cho wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.

Disclosure statement

All authors declare that they have no competing interests.

Additional information

Funding

This work was supported by a grant of the Korea Healthcare Technology R&D Project [HI15C1972010015 and HI18C19990200], Ministry of Health Welfare & Family affairs, Republic of Korea and by Basic Science Research program through National Research Foundation of Korea [NRF-2017R1D1A1B03033900 and NRF-2017R1D1A1B3031542].