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.