Abstract
Micro-RNAs (miRNAs) regulate diverse cellular processes such as cell differentiation, proliferation and apoptosis. Mutation in miRNAs results in various pathological conditions such as inflammation, viral infections, neurodegeneration, autoimmunity, and so on. We have evaluated the association of miR-146aC > G (rs2910164), miR-149T > C (rs2292832), miR-196a2T > C (rs11614913), and miR-499A > G (rs3746444) among patients with recurrent miscarriage (RM) and controls from North India. All the 200 patients with RM reported to experience at least 3 unexplained miscarriages before 20th week of gestation. Three hundred fertile women with no history of RMs were taken as controls. Both patients and controls were genotyped by the polymerase chain reaction amplification followed by restriction fragment length polymorphism. Variant alleles and genotypes of miR-499 A > G (Single Nucleotide Polymorphism Database [dbSNP] ID rs3746444) were found to be significant risks associated with patients having RM (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.40–2.81; P value = .0001) and controls (OR = 3.64; 95% CI = 1.33–9.94; P value = .0109). A significant susceptible effect was found at allelic level in miR-196aT > C (dbSNP ID rs11614913) and miR-499 A > G (dbSNP ID rs3746444).
Similar content being viewed by others
References
O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111–122.
Wiesen JL, Tomasi TB. Dicer is regulated by cellular stresses and interferons. Mol Immunol. 2009;46(6):1222–1228.
Chiu RW, Lo YM. Pregnancy-associated microRNAs in maternal plasma: a channel for fetal-maternal communication? Clin Chem. 2010;56(11):1656–1657.
Kotlabova K, Doucha J, Hromadnikova I. Placental-specific microRNA in maternal circulation—identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol. 2011;89(2):185–191.
Su MT, Lin SH, Chen YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update. 2011;17(6):803–812.
Ladomery MR, Maddocks DG, Wilson ID. MicroRNAs: their discovery, biogenesis, function and potential use as biomarkers in non-invasive prenatal diagnostics. Int J Mol Epidemiol Genet. 2011;2(3):253–260.
Morales-Prieto DM, Chaiwangyen W, Ospina-Prieto S, et al. MicroRNA expression profiles of trophoblastic cells. Placenta. 2012;33(9):725–734.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–233.
Iwai N, Naraba H. Polymorphisms in human pre-miRNAs. Biochem Biophys Res Commun. 2005;331(4):1439–1444.
Xu J, Hu Z, Xu Z, et al. Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population. Hum Mutat. 2009;30(8):1231–1236.
Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer. 2010;10(6):389–402.
Zhou B, Rao L, Peng Y, et al. Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy. Clin Chim Acta. 2010;411(17–18):1287–1290.
Hoffman AE, Zheng T, Yi C, et al. MicroRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res. 2009;69(14):5970–5977.
Suzuki Y, Kim HW, Ashraf M, Haider Hkh. Diazoxide potentiates mesenchymal stem cell survival via NF-ĸB-dependent miR-146a expression by targeting Fas. Am J Physiol Heart Circ Physiol. 2010;299(4):H1077–H1082.
Lin RJ, Lin YC, Yu AL. miR-149 induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells. Mol Carcinog. 2010;49(8):719–727.
Kefas B, Godlewski J, Comeau L, et al. microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is downregulated in glioblastoma. Cancer Res. 2008;68(10):3566–3572.
Thum T, Catalucci D, Bauersachs J. MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc Res. 2008; 79(4):562–570.
Eisenberg I, Eran A, Nishino I, et al. Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA. 2007;104(43):17016–17021.
Joglekar MV, Parekh VS, Hardikar AA. Islet-specific microRNAs in pancreas development, regeneration and diabetes. Indian J Exp Biol. 2011;49(6):401–408.
Jeon YJ, Choi YS, Rah H, et al. Association study of microRNA polymorphisms with risk of idiopathic recurrent spontaneous abortion in Korean women. Gene. 2012;494(2):168–173.
Fish JE, Srivastava D. MicroRNAs: opening a new vein in angiogenesis research. Sci Signal. 2009;2(52):pe1.
Kotlabova K, Doucha J, Hromadnikova I. Placental-specific microRNA in maternal circulation-identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol. 2011;89(2):185–191.
Fluhr H, Wenig H, Spratte J, et al. Non-apoptotic Fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity. Mol Hum Reprod. 2011;17(2):127–134.
Carcagno AL, Marazita MC, Ogara MF, et al. E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation. PLoS One. 2011;6(7):e21938.
Fujino T, Yamazaki Y, Largaespada DA, et al. Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox genes. Exp Hematol. 2001;29(7):856–863.
Murakami A, Ishida S, Thurlow J, et al. SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter. Nucleic Acids Res. 2001;29(7):3347–3355.
Sluijter JP, van Mil A, van Vliet P, et al. MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30(4):859–868.
Kawasaki H, Taira K. MicroRNA-196 inhibits HOXB8 expression in myeloid differentiation of HL60 cells. Nucleic Acids Symp Ser (Oxf). 2004;(48):211–212.
Makker A, Goel MM, Das V. PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol. 2012;28(3):175–181.
Vitiello D, Kodaman PH, Taylor HS. HOX genes in implantation. Semin Reprod Med. 2007;25(6):431–436.
Hornstein E, Mansfield JH, Yekta S, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005;438(7068):671–674.
Renthal NE, Chen CC, Williams KC, et al. MiR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci USA. 2010;107(48):20828–20833.
Fang Y, Kong B, Yang Q, et al. MDM2 309polymorphism is associated with missed abortion. Hum Reprod. 2009;24(6):1346–1349.
Zhong H, Wang HR, Yang S, et al. Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line. Int J Hematol. 2010;92(1):129–135.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parveen, F., Agrawal, S. Recurrent Miscarriage and Micro-RNA Among North Indian Women. Reprod. Sci. 22, 410–415 (2015). https://doi.org/10.1177/1933719114529376
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719114529376