Genetic Polymorphisms in <i>miR-604</i>A>G, <i>miR-938</i>G>A, <i>miR-1302-3</i>C>T and the Risk of Idiopathic Recurrent Pregnancy Loss

• Main Authors: Sung-Hwan Cho, Ji-Hyang Kim, Hui-Jeong An, Young-Ran Kim, Eun-Hee Ahn, Jung-Ryeol Lee, Jung-Oh Kim, Jung-Jae Ko, Nam-Keun Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: recurrent pregnancy loss; single nucleotide polymorphism (SNP); microRNA; MTHFR; GnRHR
• Online Access: https://www.mdpi.com/1422-0067/22/11/6127
• ISSN: 1661-6596; 1422-0067

The purpose of this study was to investigate whether polymorphisms in five microRNAs (miRNAs), <i>miR-604</i>A>G, <i>miR-608</i>C>G, <i>631</i>I/D, <i>miR-938</i>G>A, and <i>miR-1302-3</i>C>T, are associated with the risk of idiopathic recurrent pregnancy loss (RPL). Blood samples were collected from 388 patients with idiopathic RPL (at least two consecutive spontaneous abortions) and 227 control participants. We found the <i>miR-604</i> AG and AG + GG genotypes of <i>miR-604</i>, the <i>miR-938</i> GA and GA + AA genotypes of <i>miR-938</i>, and the <i>miR-1302-3</i>CT and CT + TT genotypes of <i>miR-1302-3</i> are less frequent than the wild-type (WT) genotypes, <i>miR-604</i>AA, <i>miR-938</i>GG, and <i>miR-1302-3</i>CC, respectively, in RPL patients. Using allele-combination multifactor dimensionality reduction (MDR) analysis, we found that eight haplotypes conferred by the miR-604/miR-608/miR-631/miR-938/miR-1302-3 allele combination, A-C-I-G-T, A-C-I-A-C, G-C-I-G-C, G-C-I-G-T, G-G-I-G-C, G-G-I-G-T, G-G-I-A-C, G-G-D-G-C, three from the <i>miR-604/miR-631/miR-938/miR-1302-3</i> allele combination, A-I-G-T, G-I-G-C, G-I-A-T, one from the <i>miR-604/miR-631/miR-1302-3</i> allele combination, G-I-C, and two from the <i>miR-604/miR-1302-3</i> allele combination, G-C and G-T, were less frequent in RPL patients, suggesting protective effects (all <i>p</i> < 0.05). We also identified the <i>miR-604</i>A>G and <i>miR-938</i>G>A polymorphisms within the seed sequence of the mature miRNAs and aligned the seed sequences with the 3′UTR of putative target genes, methylenetetrahydrofolate reductase (<i>MTHFR</i>) and gonadotropin-releasing hormone receptor (<i>GnRHR</i>), respectively. We further found that the binding affinities between <i>miR-604/miR-938</i> and the 3′UTR of their respective target genes (<i>MTHFR, GnRHR</i>) were significantly different for the common (<i>miR-604</i>A, <i>miR-938</i>G) and variant alleles (<i>miR-604</i>G, <i>miR-938</i>A). These results reveal a significant association between the <i>miR-604</i>A>G and <i>miR-938</i>G>A polymorphisms and idiopathic RPL and suggest that miRNAs can affect RPL in Korean women.