Genetika 2022 Volume 54, Issue 2, Pages: 933-946
https://doi.org/10.2298/GENSR2202933M
Full text ( 606 KB)
MiR-146a gene variant rs2910164 might be associated with coronary in-stent restenosis risk: Results from a pilot study and meta-analysis
Mihajlović Milica T. (University of Belgrade, Faculty of Biology, Belgrade, Serbia)
Savić-Veselinović Marija (University of Belgrade, Faculty of Biology, Belgrade, Serbia)
Farkić Mihajlo (“Dedinje” Cardiovascular Institute, Belgrade, Serbia)
Zeljić Katarina (University of Belgrade, Faculty of Biology, Belgrade, Serbia), katarina.zeljic@bio.bg.ac.rs
Coronary in-stent restenosis (ISR) is an adverse effect that occurs in 20-35%
of patients who have undergone percutaneous coronary intervention (PCI) with
stent implantation. The fact that not all patients will develop ISR
indicates that genetic factors contribute to ISR susceptibility. Previous
studies have reported that various micro RNA (miRNA) molecules regulate
biological processes underlying ISR development, including miR-146a which is
involved in regulation of vascular smooth muscle cells proliferation and
neointima formation. Nucleotide variants in miRNA genes can affect the
function of mature miRNAs. mir-146a rs2910164 gene variant is located in the
seed region of mature miR-146a, key region for the regulation of target
mRNAs. The current study aimed to examine the association between rs2910164
variant in mir-146a gene and coronary ISR risk in a group of Serbian
patients and to enhance the study by performing a meta-analysis. Samples of
peripheral blood were obtained from 61 patients who previously underwent PCI
with stent implantation, 25 (41%) of which had angiographically confirmed
ISR. There were no significant differences in allele and genotype
distribution of rs2910164 variant between patients with and without ISR. In
a Serbian group of patients, the analyzed variant was not associated with
the ISR risk. Results of the meta-analysis showed that heterozygous GC
genotype is associated with decreased risk to ISR (OR=0.475, P=0.006),
indicating its protective role in ISR formation.
Keywords: coronary in-stent restenosis, miR-146a, percutaneous coronary intervention, rs2910164
Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 451-03-9/2021-14/200178
Show references
BENNETT, M.R., M., O'SULLIVAN (2001): Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Pharmacol Ther., 91(2): 149-166.
BUCCHERI, D., D., PIRAINO, G., ANDOLINA, B., CORTESE (2016): Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment. J. Thorac. Dis., 8(10): E1150-E1162.
CASSESE, S., R.A., BYRNE, S., SCHULZ, HOPPMAN, J., KREUTZER, A., FEUCHTENBERGER, T., IBRAHIM, I., OTT, M., FUSARO, H., SCHUNKERT, K.L., LAUGWITZ, A., KASTRATI (2015): Prognostic role of restenosis in 10 004 patients undergoing routine control angiography after coronary stenting. Eur. Heart J., 36(2): 94-9.
CHENG, G., F.J., CHANG, Y., WANG, P.H., YOU, H.C., CHEN, W., HAN, J., WANG, N., ZHONG, Z., MIN (2019): Factors Influencing Stent Restenosis After Percutaneous Coronary Intervention in Patients with Coronary Heart Disease: A Clinical Trial Based on 1-Year Follow-Up. Med. Sci. Monit., 25: 240-247.
DONG, S., W., XIONG, J., YUAN, J., LI, J., LIU, X., XU (2013): MiRNA-146a regulates the maturation and differentiation of vascular smooth muscle cells by targeting NF-κB expression. Mol. Med. Rep., 8(2): 407-412.
FRAGOSO, J.M., J., RAMÍREZ-BELLO, M.A., MARTÍNEZ-RÍOS, M.A., PEÑA-DUQUE, R., POSADAS-SÁNCHEZ, H., DELGADILLO-RODRÍGUEZ, M., JIMÉNEZ-MORALES, C., POSADAS-ROMERO, G., VARGAS-ALARCÓN (2019): miR-196a2 (rs11614913) polymorphism is associated with coronary artery disease, but not with in-stent coronary restenosis. Inflammation Res., 68(3): 215-221.
GARERI, C., S., DE ROSSA, C., INDOLFI (2016): MicroRNAs for Restenosis and Thrombosis After Vascular Injury. Circ Res, 118(7):1170-1184.
GEBERT, L.F., I.J., MACRAE (2019): Regulation of microRNA function in animals. Nature reviews Mol Cell Biol, 20(1): 21-37.
HAMANN, L., C., GLAESER, S., SCHULZ, M., GROSS, A., FRANKE, U., NÖTHLINGS, R.R., SCHUMANN (2014): A micro RNA-146a polymorphism is associated with coronary restenosis. Int. J. Immunogenet, 41(5):393-396.
HUFFAKER, T., HU, R., RUNTSCH, M., BAKE, E., CHEN, X., ZHAO, J., ROUND, J., BALTIMORE, R., O’CONNELL (2012): Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity. Cell Reports, 2: 1697-1709.
JAZDZEWSKI, K., E.L., MURRAY, K., FRANSILLA, B., JARZAB, D.R., SCHOENBERG, A., DE LA CHAPELLE (2008): Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Nac. Acad. Sci. USA, 105(20): 7269-7274.
JAZDZEWSKI, K., S., LIYANARACHCHI, M., SWIERNIAK, J., PACHUCKI, M.D., RINGEL, B., JARZAB, A., DE LA CHAPELLE (2009): Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc. Nac. Acad. Sci. USA, 106(5):1502-1505.
KIM, V.N., J., HAN, M.C., SIOMI (2009): Biogenesis of small RNAs in animals. Nat. Rev. Mol. Cell. Biol., 10(2):126-139.
LEOPOLD, J.A., J., LOSCALZO (2018): Emerging Role of Precision Medicine in Cardiovascular Disease. Circ. Res., 122(9): 1302-1315.
LI, Y., H., CHO, F., WANG, O., CANELA-XANDRI, C., LUO, K., RAWLIK, S., ARCHACKI C., XU, A., TENESA, Q., CHEN, Q., WANG (2020): Epistasis of Cardiovascular Risk Genomic Variants From Genome-Wide Association Studies. J. Am. Heart Assoc., 9:e014146.
LIU, S., Y., YANG, S., JIANG, N., TANG, J., TIAN, M., PONNUSAMY, M.A., TARIQ, Z., LIAN, H., XIN, T., YU (2018): Understanding the role of non-coding RNA (ncRNA) in stent restenosis. Atherosclerosis, 272: 153-161.
MARSCHNER, D., M., FALK, N.R., JAVORNICZKY, K., HANKE-MÜLLER, J., RAWLUK, A., SCHMITT-GRAEFF, F., SIMONETTA, E., HARING, S., DICKS, M., KU, S., DUQUESNE, K., AUMANN, D., RAFEI-SHAMSABADI, F., MEISS, P., MARSCHNER, M., BOERRIES, R.S., NEGRIN, J., DUYSTER, R., ZEISER, N., KÖHLER (2020): MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors. JCI Insight, 5(6): e132334.
MARTORELL-MARUGAN, J., D., TORO-DOMINGUEZ, M.E., ALARCON-RIQUELME, P., CARMONA-SAEZ (2017). MetaGenyo: a web tool for meta-analysis of genetic association studies. BMC bioinformatics, 18(1): 563.
MOSES, J.W., M.B., LEON, J.J., POPMA, P.J., FITZGERALD, D.R., HOLMES, C., O'SHAUGHNESSY, R.P., CAPUTO, D.J., KEREIAKES, D.O., WILLIAMS, P.S., TEIRSTEIN, J.L., JAEGER, R.E., KUNTZ, SIRIUS INVESTIGATORS (2003): Sirolimus eluting stents versus standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med., 349(14): 1315-1323.
O'BRIEN, J., H., HAYDER, Y., ZAYED, C., PENG (2018): Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne), 9:402.
PLEVA, L., P., KUKLA, O., HLINOMAZ (2018): Treatment of coronary in-stent restenosis: a systematic review. J. Geriatr. Cardiol., 15(2):173-184.
PRICE, A.L., C.C.A., SPENCER, P., DONNELLY (2015): Progress and promise in understanding the genetic basis of common diseases. Proc. Biol. Sci., 282(1821):20151684.
RAMKARAN, P., S., KHAN, A., PHULUKDAREE, D., MOODLEY, A.A., CHUTURGOON (2014): miR-146a Polymorphism Influences Levels of miR-146a, IRAK-1, and TRAF-6 in Young Patients with Coronary Artery Disease. Cell Biochem. Biophys., 68(2): 259-266.
RUSCA, N., S., MONTICELLI (2011): MiR-146a in immunity and disease. Mol. Biol. Int., 2011(2011): 437301.
RYAN, B.M., A.I., ROBLES, C.C., HARRIS (2010): Genetic variation in microRNA networks: the implication for cancer research. Nat. Rev. Cancer, 10(6):389-402.
SAUNDERS, M.A., H., LIANG, W.H., LI (2007): Human polymorphism at microRNAs and microRNA target sites. Proc. Nac. Ac. Sci. USA, 104(9):3300-3305.
STONE, G.W., S.G., ELLIS, D.A., COX, J., HERMILLER, C., O'SHAUGHNESSY, J.T., MANN, M., TURCO, R., CAPUTO, P., BERGIN, J., GREENBERG, J.J., POPMA, M.E., RUSSELL, TAXUS-IV INVESTIGATORS (2004): A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N. Engl. J. Med., 350(3):221-231.
SUN, S.G., B., ZHENG, M., HAN, X.M., FANG, H.X., LI, S.B., MIAO, M., SU, Y., HAN, H.J., SHI, J.K., WEN (2010): miR-146a and Kruppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation. EMBO Rep., 12(1): 56-62.
VALENTINE, J. C., T. D, PIGOTT, H. R., ROTHSTEIN (2010): How many studies do you need? A primer on statistical power for meta-analysis. JEBS, 35(2): 215-247.
XIONG, X.D., M., CHO, X.P., CAI, J., CHENG, X., JING, J.M., CEN, X., LIU, X.L., YANG, Y., SUH (2014): A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat. Res., 761:15-20.
ZHANG, H., Q., ZHANG, Y., LIU, T., XUE (2020): miR-146a and miR-146b predict increased restenosis and rapid angiographic stenotic progression risk in coronary heart disease patients who underwent percuataneous coronary intervention. Ir. J. Med. Sci., 189(2): 467-474.