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

Sung Hwan Cho, Ki Wha Chung, Jung Oh Kim, Hyogeun Jang, Jung Ki Yoo, Youngsok Choi, Jung Jae Ko, Ji Hyang Kim, Yoshihiro Nishi, Toshihiko Yanase, Woo Sik Lee, Nam Keun Kim
European Journal of Obstetrics, Gynecology, and Reproductive Biology 2016, 202: 14-9

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.

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