Cho Sung Hwan, Chung Ki Wha, Kim Jung Oh, Jang Hyogeun, Yoo Jung Ki, Choi Youngsok, Ko Jung Jae, Kim Ji Hyang, Nishi Yoshihiro, Yanase Toshihiko, Lee Woo Sik, Kim Nam Keun
Department of Biomedical Science, College of Life Science, CHA University, Seongnam, 463-400, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, 463-712, South Korea.
Department of Biological Science, College of Natural Science, Kongju National University, Gongju, South Korea.
Eur J Obstet Gynecol Reprod Biol. 2016 Jul;202:14-9. doi: 10.1016/j.ejogrb.2016.04.009. Epub 2016 Apr 25.
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).
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.
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).
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.
本研究旨在调查韩国复发性植入失败（RIF）患者中微小RNA多态性（miR-146aC>G、miR-149T>C、miR-196a2T>C和miR-499A>G）的相关性。
我们对354名韩国女性进行了病例对照研究：120例RIF患者和234名健康对照者，后者至少有一次活产且无流产史。
miR-146aCG+GG/miR-196a2CC联合基因型在患者中比在对照者中更常见（P<0.05），且明显增加了易感性。相反，基于基因型的多因素降维分析显示，G-T-T-A（miR-146a/-149/-196a2/-499）和G-T-T推断基因型（miR-146a/-149/-196a2）在患者中明显较少见，这表明可能具有潜在的保护作用。miR-146a的GG纯合子的表达明显低于miR-146a-3p的前体、成熟体和序列的CC纯合子的表达（各P<0.05）。miR-196a2的CC纯合子的表达也低于miR-196a2-3p成熟序列的TT纯合子的表达（P<0.05）。
这些结果表明，miR-146a和miR-196a2中的多态性可能会改变其靶mRNA的表达。我们的研究结果表明，miR-146aC>G、miR-196a2T>C的表达水平以及miR-146a、miR-196a2、miR-149之间假定的基因-基因相互作用可能参与了韩国女性RIF的发生发展。
