MTHFR 3'-untranslated region polymorphisms contribute to recurrent pregnancy loss risk and alterations in peripheral natural killer cell proportions.

OBJECTIVE: To identify the associations between polymorphisms of the 3'-untranslated region (UTR) of methylenetetrahydrofolate reductase ( MTHFR ) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women.

METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C>A, 4869C>G, 5488C>T, and 6685T>C 3'-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry.

RESULTS: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178-0.994; p =0.048) for RPL. Analysis of variance revealed that MTHFR 4869C>G was associated with altered CD56+ natural killer cell percentages (CC, 17.91%±8.04%; CG, 12.67%±4.64%; p =0.024) and folate levels (CC, 12.01±7.18 mg/mL; CG, 22.15±26.25 mg/mL; p =0.006).

CONCLUSION: Variants in the 3'-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.