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
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 idi...
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doaj-7c46c5b9c0264534b7824cb8baca7cf72021-06-30T23:28:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01226127612710.3390/ijms22116127Genetic 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 LossSung-Hwan Cho0Ji-Hyang Kim1Hui-Jeong An2Young-Ran Kim3Eun-Hee Ahn4Jung-Ryeol Lee5Jung-Oh Kim6Jung-Jae Ko7Nam-Keun Kim8Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaCHA Bundang Medical Center, Department of Obstetrics and Gynecology, School of Medicine, CHA University, Seongnam 13496, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaCHA Bundang Medical Center, Department of Obstetrics and Gynecology, School of Medicine, CHA University, Seongnam 13496, KoreaCHA Bundang Medical Center, Department of Obstetrics and Gynecology, School of Medicine, CHA University, Seongnam 13496, KoreaDepartment of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaThe 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.https://www.mdpi.com/1422-0067/22/11/6127recurrent pregnancy losssingle nucleotide polymorphism (SNP)microRNAMTHFRGnRHR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 International Journal of Molecular Sciences recurrent pregnancy loss single nucleotide polymorphism (SNP) microRNA MTHFR GnRHR |
author_facet |
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 |
author_sort |
Sung-Hwan Cho |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
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. |
topic |
recurrent pregnancy loss single nucleotide polymorphism (SNP) microRNA MTHFR GnRHR |
url |
https://www.mdpi.com/1422-0067/22/11/6127 |
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