Abstract
Single-nucleotide variant (SNV) is a single base mutation at a specific location in the genome and may play an import role in epilepsy pathophysiology. The aim of this study was to review case–control studies that have investigated the relationship between SNVs within microRNAs (miRs) sequences or in their target genes and epilepsy susceptibility from January 1, 2010 to October 31, 2020. Nine case–control studies were included in the present review. The mainly observed SNVs associated with drug-resistant epilepsy (DRE) risk were SNVs n.60G > C (rs2910164) and n.-411A > G (rs57095329), both located at miR-146a mature sequence and promoter region, respectively. In addition, the CC haplotype (rs987195-rs969885) and the AA genotype at rs4817027 in the MIR155HG/miR-155 tagSNV were also genetic susceptibility markers for early-onset epilepsy. MiR-146a has been observed as upregulated in human astrocytes in epileptogenesis and it regulates inflammatory process through NF-κB signaling by targeting tumor necrosis factor-associated factor 6 (TRAF6) gene. The SNVs rs2910164 and rs57095329 may modify the expression level of mature miR-146a and the risk for epilepsy and SNVs located at rs987195-rs969885 haplotype and at rs4817027 in the MIR155HG/miR-155 tagSNV could interfere in the miR-155 expression modulating inflammatory pathway genes involved in the development of early-onset epilepsy. In addition, SNVs rs662702, rs3208684, and rs35163679 at 3′untranslated region impairs the ability of miR-328, let-7b, and miR-200c binding affinity with paired box protein PAX-6 (PAX6), BCL2 like 1 (BCL2L1), and DNA methyltransferase 3 alpha (DNMT3A) target genes. The SNV rs57095329 might be correlated with DRE when a larger number of patients are evaluated. Thus, we concluded that the main drawback of most of studies is the small number of individuals enrolled, which lacks sample power.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The data and material will be available on request.
Abbreviations
- 3′-UTR:
-
3′untranslated region
- AARS:
-
Alanyl-tRNA synthetase
- ALDH7A1 :
-
Aldehyde dehydrogenase 7 family member A1
- ALG13 :
-
Asparagine-linked glycosylation 13
- BCL2L1 :
-
BCL2 like 1
- CI:
-
Confidence interval
- DNA:
-
Deoxyribonucleic acid
- DNMT3A :
-
DNA methyltransferase 3 alpha
- DRE:
-
Drug-resistant epilepsy
- NF-kB :
-
Factor nuclear kappa B
- GABA:
-
Gamma-aminobutyric acid
- IFN-ϒ :
-
Interferon-gamma
- IL-1 :
-
Interleukin 1
- IL-1β :
-
Interleukin 1 beta
- IRAK1 :
-
Interleukin 1 receptor associated kinase 1
- ILAE:
-
International league against epilepsy
- MTLE:
-
Mesial temporal lobe epilepsy
- miRs:
-
MicroRNAs
- NMDA:
-
N-Methyl-D-aspartate
- OR:
-
Odds ratio
- OMIM:
-
Online mendelian inheritance in man
- PAX-6 :
-
Paired box protein PAX-6
- PCR:
-
Polymerase chain reaction
- RISC:
-
RNA-induced silencing complex
- RNA:
-
Ribonucleic acid
- SNVs:
-
Single-nucleotide variants
- SCN1A :
-
Sodium voltage-gated channel alpha subunit 1
- SCN2A:
-
Sodium voltage-gated channel alpha subunit 2
- SCN1B :
-
Sodium voltage-gated channel beta Subunit 1
- TlE:
-
Temporal lobe epilepsy
- TNF-α :
-
Tumor necrosis factor alpha
- TRAF6:
-
Tumor necrosis factor receptor (TNFR)-associated actor 6
- WHO:
-
World Health Organization
References
Asadi-Pooya AA, Stewart GR, Abrams DJ, Sharan A (2017) Prevalence and incidence of drug-resistant mesial temporal lobe epilepsy in the United States. World Neurosurg 99:662–666. https://doi.org/10.1016/j.wneu.2016.12.074
Ashhab MU, Omran A, Kong H, Gan N, He F, Peng J, Yin F (2013) Expressions of tumor necrosis factor alpha and MicroRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy. J Mol Neurosci 51:950–958. https://doi.org/10.1007/s12031-013-0013-9
Balosso S, Maroso M, Sanchez-Alavez M, Ravizza T, Frasca A, Bartfai T, Vezzani A (2008) A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1b. Brain 131:3256–3265. https://doi.org/10.1093/brain/awn271
Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233. https://doi.org/10.1016/j.cell.2009.01.002
Beghi E (2020) The epidemiology of epilepsy. Neuroepidemiology 54:185–191. https://doi.org/10.1159/000503831
Boschiero MN, Camporeze B, Santos JS, Costa LB, Bonafé GA, Queiroz LS, Roost DV, Marson FAL et al (2020) The single nucleotide variant n.60G>C in the microRNA-146a associated with susceptibility to drug-resistant.epilepsy. Epilepsy Res 162:1–8. https://doi.org/10.1016/j.eplepsyres.2020.106305
Brennan GP, Henshall DC (2018) MicroRNAs in the pathophysiology of epilepsy. Neurosci Lett 667:47–52. https://doi.org/10.1016/j.neulet.2017.01.017
Cui L, Tao H, Wang Y, Liu Z, Xu Z, Zhou H, Cai Y, Yao L (2015) A functional polymorphism of the microRNA-146a gene is associated with susceptibility to drug-resistant epilepsy and seizures frequency. Seizure 27:60–65. https://doi.org/10.1016/j.seizure.2015.02.032
Dabhi B, Mistry KN (2014) In silico analysis of single nucleotide polymorphism (SNP) in human TNF-α gene. Meta Gene 2:586–595. https://doi.org/10.1016/j.mgene.2014.07.005
Dehghani R, Rahmani F, Rezaei N (2018) MicroRNA in Alzheimer’s disease revisited: implications for major neuropathological mechanisms. Rev Neurosci 29:161–182. https://doi.org/10.1515/revneuro-2017-0042
Dos Santos M, Stur E, Maia LL, Agostini LP, Peterle GT, Mendes SO, Tajara EH, de Carvalho MB et al (2013) Genetic variability of inflammatory genes in the Brazilian population. Genet Test Mol Biomarkers 17:844–848. https://doi.org/10.1089/gtmb.2013.0264
Duan R, Pak C, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16:1124–1131. https://doi.org/10.1093/hmg/ddm062
Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO in https://www.who.int/mental_health/neurology/epilepsy/report_2019/en/. Accessed 30 March 2020.
Falco-Walter JJ, Scheffen IE, Fisher RS (2018) The new definition and classification of seizures and epilepsy. Epilepsy Res 139:73–79. https://doi.org/10.1016/j.eplepsyres.2017.11.015
Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Siva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430. https://doi.org/10.1038/nn.2514
Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114. https://doi.org/10.1038/nrg2290
Fisher RS, Acevedo C, Arzimanoglou A et al (2014) A practical clinical definition of epilepsy. Epilepsia 55:475–482. https://doi.org/10.1111/epi.12550
Haixia D, Hairong D, Weixian C, Min Y, Qiang W, Hang X (2012) Lack of association of polymorphism in miRNA-196a2 with Parkinson’s disease risk in a Chinese population. Neurosci Lett 514:194–197. https://doi.org/10.1016/j.neulet.2012.02.093
Hata A, Kashima R (2016) Dysregulation of microRNA biogenesis machinery in cancer. Crit Rev Biochem Mol Biol 51:121–134. https://doi.org/10.3109/10409238.2015.1117054
He M, Liu Y, Wang X, Zhang MQ, Hannon GJ, Juang ZJ (2012) Cell-type-based analysis of microRNA profiles in the mouse brain. Neuron 73:35–48. https://doi.org/10.1016/j.neuron.2011.11.010
Henshall DC, Clark RS, Adelson PD, Chen M, Watkins SC, Simon RP (2000) Alterations in bcl-2 and caspase gene family protein expression in human temporal lobe epilepsy. Neurology 55:250–257. https://doi.org/10.1212/wnl.55.2.250
Hildebrand MS, Dahl HH, Damiano JA, Smith RJ, Scheffer IE, Berkovic SF (2013) Recent advances in molecular genetics of epilepsy. J Med Genet 50:271–279. https://doi.org/10.1136/jmedgenet-2012-101448
Horvitz HR, Sulston JE (1980) Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics 96:435–454
Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X (2009) MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 183:2150–2158. https://doi.org/10.4049/jimmunol.0900707
Iori V, Iyer AM, Ravizza T, Beltrame L, Paracchini L, Marchini S, Cerovic M, Hill C et al (2017) Blockade of the IL-1R1/TLR4 pathway mediates disease-modification therapeutic effects in a model of acquired epilepsy. Neurobiol Dis 99:12–23. https://doi.org/10.1016/j.nbd.2016.12.007
Issac MSM, Girgis M, Haroun M, Shalaby A (2015) Association of genetic polymorphism of pre-microRNA-146a rs2910164 and serum high-mobility group Box 1 with febrile seizures in Egyptian children. J Child Neurol 30:437–444. https://doi.org/10.1177/0883073814550312
Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature mir expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274. https://doi.org/10.1073/pnas.0802682105
Johnson EL (2019) Seizures and epilepsy. Med Clin North Am 103:309–324. https://doi.org/10.1016/j.mcna.2018.10.002
Jovicic A, Roshan R, Moisoi N, Pradervand S, Moser R, Pillai B, Luthi-Carter R (2013) Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J Neurosci 33:5127–5137. https://doi.org/10.1523/JNEUROSCI.0600-12.2013
Kosik KS (2006) The neuronal microRNA system. Nat Rev Neurosci 7:911–920. https://doi.org/10.1038/nrn2037
Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610. https://doi.org/10.1038/nrg2843
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739. https://doi.org/10.1016/s0960-9822(02)00809-6
Lapalme-Remis S, Cascino GD (2016) Imaging for adults with seizures and epilepsy. Continuum (Minneap Minn) 22:1451–1479. https://doi.org/10.1212/CON.0000000000000370
Lee RC, Ambros V (2001) An extensive class of small RNAs in caenorhabditis elegans. Science 294:862–864. https://doi.org/10.1126/science.1065329
Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20. https://doi.org/10.1016/j.cell.2004.12.035
Li T, Kuang Y, Li B (2016a) The genetic variants in 3’ untranslated region of voltage-gated sodium channel alpha 1 subunit gene affect the mRNA-microRNA interactions and associate with epilepsy. BMC Genet 17:111. https://doi.org/10.1186/s12863-016-0417-y
Li Y, Wang J, Jiang C, Zheng G, Lu X, Guo H (2016b) Association of the genetic polymorphisms in pre-microRNAs with risk of childhood epilepsy in a Chinese population. Seizure 40:21–26. https://doi.org/10.1016/j.seizure.2016.04.011
Lin WJ, Liu Z-J, Xu L, Shi H-Q, Yi Y-W, He Y-H, Liao N, W-P, (2017) Epilepsy-associated genes. Seizure 44:11–20. https://doi.org/10.1016/j.seizure.2016.11.030
Lu TX, Rothenberg ME (2018) MicroRNA. J Allergy Clin Immunol 141:1202–1207. https://doi.org/10.1016/j.jaci.2017.08.034
Lubin FD, Ren Y, Xu X, Anderson AE (2007) Nuclear factor-jB regulates seizure threshold and gene transcription following convulsant stimulation. J Neurochem 103:1381–1395. https://doi.org/10.1111/j.1471-4159.2007.04863.x
Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C, Rheinheimer S, Stahler C et al (2016) Distribution of miRNA expression across human tissues. Nucleic Acids Res 44:3865–3877. https://doi.org/10.1093/nar/gkw116
Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283:31315–31322. https://doi.org/10.1074/jbc.M805371200
Ma Y (2018) The Challenge of microRNA as a Biomarker of Epilepsy. Curr Neuropharmacol 16:37–42. https://doi.org/10.2174/1570159X15666170703102410
Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27:435–448. https://doi.org/10.1016/j.molcel.2007.07.015
Manna I, Labate A, Munoli L, Pantusa M, Ferlazzo E, Aguglia U, Quattrone A, Gambardella A (2013) Relationship between genetic variant in pre-microRNA-146a and genetic predisposition to temporal lobe epilepsy: a case–control study. Gene 516:181–183. https://doi.org/10.1016/j.gene.2012.09.137
Manna I, Labate A, Borzi G, Munoli L, Cavalli SM, Sturniolo M, Quattrone A, Gambardella A (2016) An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample. Neurol Sci 37:1335–1339. https://doi.org/10.1007/s10072-016-2597-7
McKiernan RC, Jimenez-Mateos EM, Bray I, Engel T, Brennan GP, Michalak STZ, Moran C et al (2012) Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. PLoS ONE 7:e35921. https://doi.org/10.1371/journal.pone.0035921
Meister G (2013) Argonaute proteins: functional insights and emerging roles. Nat Rev Genet 14:447–459. https://doi.org/10.1038/nrg3462
Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, Constantine-Paton M, Horvitz HR (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68. https://doi.org/10.1186/gb-2004-5-9-r68
Panjwani N, Wilson MD, Addis L, Crosbie J, Wirrell E, Auvin S, Caraballo RH, Kinali M et al (2016) A microRNA-328 binding site in PAX6 is associated with centrotemporal spikes of rolandic epilepsy. Ann Clin Transl Neurol 3:512–522. https://doi.org/10.1002/acn3.320
Paraboschi EM, Soldà G, Gemmati D, Orioli E, Zeri G, Benedetti MD, Salviati A, Barizzone N et al (2011) Genetic association and altered gene expression of mir-155 in multiple sclerosis patients. Int J Mol Sci 12:8695–8712. https://doi.org/10.3390/ijms12128695
Parikh S, Nordi JR, De Vivo DC (2015) Epilepsy in the setting of inherited metabolic and mitochondrial disorders. In: Wyllie E (ed) Wyllie´s treatment of epilepsy: principles and practice, 5th edn. Lippincott Williams & Wilkins, Philadelphia, PA, USA, pp 375–382
Peng J, Omran A, Ashhab MU, Kong H, Gan N, He F, Yin F (2013) Expression patterns of miR-124, miR-134, miR-132, and miR-21 in an immature rat model and children with mesial temporal lobe epilepsy. J Mol Neurosci 50:291–297. https://doi.org/10.1007/s12031-013-9953-3
Perucca P, Perucca E (2019) Identifying mutations in epilepsy genes: impact on treatment selection. Epilepsy Res 152:18–30. https://doi.org/10.1016/j.eplepsyres.2019.03.001
Quinlan S, Kenny A, Medina M, Engel T, Jimenez-Mateos EM (2017) MicroRNAs in neurodegenerative diseases. Int Rev Cell Mol Biol 334:309–343. https://doi.org/10.1016/bs.ircmb.2017.04.002
Sanuki R, Onishi A, Koike C, Muramatsu R, Watanabe S, Muranishi Y, Irie S, Uneo S et al (2011) miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression. Nat Neurosci 14:1125–1134. https://doi.org/10.1038/nn.2897
Saunders MA, Liang H, Li WH (2007) Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA 104:3300–3305. https://doi.org/10.1073/pnas.0611347104
Schaefer A, O’Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, Greengard P (2007) Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 204:1553–1558. https://doi.org/10.1084/jem.20070823
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S (2017) ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:512–521. https://doi.org/10.1111/epi.13709
Shao NY, Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Li N, Chen W, Khaitovich P (2010) Comprehensive survey of human brain microRNA by deep sequencing. BMC Genomics 11:409. https://doi.org/10.1186/1471-2164-11-409
Shibata M, Nakao H, Kiyonari H, Abe T, Aizawa S (2011) MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors. J Neurosci 31:3407–3422. https://doi.org/10.1523/jneurosci.5085-10.2011
Singh N, Vijayanti S, Saha L (2018) Targeting crosstalk between Nuclear fator (erythroid-derived 2) - like 2 - and Nuclear fator kappa beta pathway by Nrf2 activator Dimethyl Fumarate in epileptogenesis. Int J Neurosci 128:987–994. https://doi.org/10.1080/00207454.2018.1441149
Sood P, Krek A, Zavolan M, Macino G, Rajewsky N (2006) Cell-type-specific signatures of microRNAs on target mRNA expression. Proc Natl Acad Sci USA 103:2746–2751. https://doi.org/10.1073/pnas.0511045103
Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486. https://doi.org/10.1073/pnas.0605298103
Tan CL, Plotkin JL, Veno MT, Schimmelmann MV, Feinberg P, Mann S, Handler A, Kjems J et al (2013) MicroRNA-128 governs neuronal excitability and motor behavior in mice. Science 342:1254–1258. https://doi.org/10.1126/science.1244193
Tao H, Cui L, Li Y, Zhou X, Ma G, Yao L, Fu J, Li W (2015) Association of Tag SNPs and Rare CNVs of the MIR155HG/miR-155 Gene with Epilepsy in the Chinese Han Population. Biomed Res Int 2015:1–8. https://doi.org/10.1155/2015/837213
Toledrano M, Pittock SJ (2015) Autoimmune epilepsy. Semin Neurol 35:245–258. https://doi.org/10.1055/s-0035-1552625
Vezzani A (2014) Epilepsy and inflammation in the brain: overview and pathophysiology. Epilepsy Curr 14:3–7. https://doi.org/10.5698/1535-7511-14.s2.3
Vezzani A, Fujinami RS, White HS, Preux P-M, Blümcke I, Sander JW, Löscher W (2016) Infections, inflammation and epilepsy. Acta Neuropathol 131:211–234. https://doi.org/10.1007/s00401-015-1481-5
Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, Binaglia M, Corsini E et al (2003) Interleukin-1 enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of linases. J Neurosci 23:8692–8700. https://doi.org/10.1523/JNEUROSCI.23-25-08692.2003
Wang J, Lin Z-J, Liu L, Xu H-Q, Shi Y-W, Yi Y-H, He N, Liao W-P (2017a) Epilepsy-associated genes. Seizure 44:11–20. https://doi.org/10.1016/j.seizure.2016.11.030
Wang Y, Yang Z, Le W (2017b) Tiny but mighty: promising roles of microRNAs in the diagnosis and treatment of Parkinson’s disease. Neurosci Bull 33:543–551. https://doi.org/10.1007/s12264-017-0160-z
Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234. https://doi.org/10.1038/ncb0309-228
Xiao W, Wu Y, Wang J, Luo Z, Long L, Na D, Ning S, Zeng Y et al (2019) Network and pathway-based analysis of single-nucleotide polymorphism of miRNA in temporal lobe Epilepsy. Mol Neurobiol 56:7022–7031. https://doi.org/10.1007/s12035-019-1584-4
Yan Y, Xie R, Zhang Q, Zhu X, Han J, Xia R (2017) Bcl-xL/Bak interaction and regulation by miRNA let-7b in the intrinsic apoptotic pathway of stored platelets. Platelets 30:1–6. https://doi.org/10.1080/09537104.2017.1371289
Zhang H, Qu Y, Wang A (2018) Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced status epilepticus in rats by nuclear factor-κB pathway. Mol Med Rep 17:5356–5361. https://doi.org/10.3892/mmr.2018.8465
Zhou Q, Hou S, Liang L, Li X, Tan X, Wei L, Lei B, Kijlstra A et al (2014) MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet’s disease and Vogt-Koyanagi-Harada syndrome. Ann Rheum Dis 73:170–176. https://doi.org/10.1136/annrheumdis-2012-201627
Zhu Q, Wang L, Zhang Y, Zhao FH, Luo J, Xiao Z, Chen GJ, Wang XF (2012) Increased expression of DNA methyltransferase 1 and 3a in human temporal lobe epilepsy. J Mol Neurosci 46:420–426. https://doi.org/10.1007/s12031-011-9602-7
Funding
The financial support provided for this work by the São Paulo Research Foundation (FAPESP) scholarship# 2018/12057-0, and National Council for Scientific and Technological Development (CNPq) scholarship#149884/2019-2, are gratefully acknowledged.
Author information
Authors and Affiliations
Contributions
Conception and design: MMO; acquisition of data: RPB, MNB, BC; analyses and interpretation of data: MMO, FALM, PHPA; statistical analyses: FALM; drafting of the manuscript: RPB, MMO; study supervision: MMO. All authors were involved in revision of the manuscript and have approved the final version.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics Approval
This study was approved by the Ethic Committee of Universidade São Francisco (USF) (CAAE: 90786718.1.0000.5514). We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
Consent for Publication
All the authors gave the consent for publication.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Buainain, R.P., Boschiero, M.N., Camporeze, B. et al. Single-Nucleotide Variants in microRNAs Sequences or in their Target Genes Might Influence the Risk of Epilepsy: A Review. Cell Mol Neurobiol 42, 1645–1658 (2022). https://doi.org/10.1007/s10571-021-01058-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-021-01058-7