Association of miR-146aC>G, miR-149C>T, miR-196a2T>C, and miR-499A>G polymorphisms with risk of recurrent implantation failure in Korean women.

Objective: The aim of this study was to investigate the association of microRNA polymorphisms (miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G) in Korean patients with recurrent implantation failure (RIF).

Methods: We conducted a case-control study of 354 Korean women: 120 patients with RIF and 234 healthy controls with at least one live birth and no history of pregnancy loss.

Results: The combined miR-146aCG+GG/miR-196a2CC genotype was more frequent in patients than in controls (P<0.05), and apparently conferred increased susceptibility. Conversely, genotype-based multifactor dimensionality reduction analysis, revealed that the G-T-T-A (miR-146a/-149/-196a2/-499) and G-T-T inferred genotypes (miR-146a/-149/-196a2) were significantly less frequent in patients, which suggested potential protective effects. The expression of miR-146a for the GG homozygote was significantly lower (P<0.05) than expression of the CC homozygote from both the pre, mature and sequences of miR-146a-3p (P<0.05 each). The expression of miR-196a2 for the CC homozygote was also lower than the TT homozygote from the mature sequence of miR-196a2-3p (P<0.05).

Conclusions: These results suggest that the polymorphisms in miR-146a and miR-196a2 could alter their target mRNA expression. Our findings suggest that expression levels of miR-146aC>G, miR-196a2T>C and putative gene-gene interaction between miR-146a, miR-196a2, miR-149 may be involved in RIF development in Korean women.