Association of methionine synthase and thymidylate synthase genetic polymorphisms with idiopathic recurrent pregnancy loss

Capsule:
The MTR 2756AA and MTR 2756A–TS 6bp allele combination may contribute to prevalence of recurrent pregnancy loss (RPL) in Korean women.

Authors:
Ji Hyang Kim, M.D., Young Joo Jeon, M.S., Bo Eun Lee, B.S., Hojeong Kang, M.D., Ji Eun Shin, M.D., Dong Hee Choi, M.D., Ph.D., Woo Sik Lee, M.D., Ph.D., Nam Keun Kim, Ph.D.

Volume 99, Issue 6, Pages 1674-1680.e3, May 2013

Abstract:

Objective:
To investigate the association between one-carbon metabolism and recurrent pregnancy loss (RPL), we examined polymorphisms in four genes: methionine synthase (MTR); methionine synthase reductase (MTRR); methylenetetrahydrofolate dehydrogenase 1 (MTHFD1); and thymidylate synthase (TS). One-carbon metabolism is important for maintaining pregnancy and the enzymes codified by these genes are relevant in this metabolic pathway.

Design:
Case-control study.

Setting:
An urban university-based hospital in South Korea.

Patient(s):
A cohort of 353 RPL patients (3.09 ± 1.65 pregnancy losses) and 226 controls.

Intervention(s):
None.

Main Outcome Measure(s):
Genotyping was assessed by polymerase chain reaction–restriction fragment length polymorphism assay. We examined polymorphisms in four genes: methionine synthase (MTR); methionine synthase reductase (MTRR); methylenetetrahydrofolate dehydrogenase 1 (MTHFD1); and thymidylate synthase (TS).

Result(s):
The MTR 2756AA polymorphism was associated with RPL. Gene-gene interaction analysis revealed that the frequency of the MTR 2756A-TS 6bp allele combination was significantly higher in RPL.

Conclusion(s):
Based on these results, we propose that the MTR 2756AA genotype and MTR 2756A-TS 6bp allele combination are possible predisposing factors for RPL development in Korean women.

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