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

Abstract

Objective: To investigate the association between one-carbon metabolism and recurrent pregnancy loss (RPL). One-carbon metabolism is important for maintaining pregnancy, and the enzymes codified by these genes are relevant to 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 control subjects.

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 6-bp allele combination was significantly higher in RPL.

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