The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A

被引:15
作者
Strafella, Claudia [1 ,2 ]
Errichiello, Valeria [1 ]
Caputo, Valerio [1 ]
Aloe, Gianluca [3 ]
Ricci, Federico [3 ]
Cusumano, Andrea [3 ]
Novelli, Giuseppe [2 ]
Giardina, Emiliano [1 ,2 ]
Cascella, Raffaella [1 ,4 ]
机构
[1] Santa Lucia Fdn, Mol Genet Lab UILDM, I-00142 Rome, Italy
[2] Tor Vergata Univ, Dept Biomed & Prevent, I-00133 Rome, Italy
[3] Tor Vergata Univ, UOSD Retinal Pathol PTV Fdn Policlin, I-00133 Rome, Italy
[4] Catholic Univ Our Lady Good Counsel, Dept Biomed Sci, Tirana 1000, Albania
关键词
AMD; miRNAs; epigenetics; susceptibility; inflammation; choroidal neovascularization; neurodegeneration; SINGLE-NUCLEOTIDE POLYMORPHISM; PIGMENT EPITHELIAL-CELLS; PRECISION MEDICINE; MICRORNA-146A; MIR-146A; GENE; MIR-27A; ARMS2; RISK;
D O I
10.3390/ijms20071578
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The complex interplay among genetic, epigenetic, and environmental variables is the basis for the multifactorial origin of age-related macular degeneration (AMD). Previous results highlighted that single nucleotide polymorphisms (SNPs) of CFH, ARMS2, IL-8, TIMP3, SLC16A8, RAD51B, VEGFA, and COL8A1 were significantly associated with the risk of AMD in the Italian population. Given these data, this study aimed to investigate the impact of SNPs in genes coding for MIR146A, MIR31, MIR23A, MIR27A, MIR20A, and MIR150 on their susceptibility to AMD. Nine-hundred and seventy-six patients with exudative AMD and 1000 controls were subjected to an epigenotyping analysis through real-time PCR and direct sequencing. Biostatistical and bioinformatic analysis was performed to evaluate the association with susceptibility to AMD. These analyses reported that the SNPs rs11671784 (MIR27A, G/A) and rs2910164 (MIR146A, C/G) were significantly associated with AMD risk. Interestingly, the bioinformatic analysis showed that MIR27A and MIR146A take part in the angiogenic and inflammatory pathways underlying AMD etiopathogenesis. Thus, polymorphisms within the pre-miRNA sequences are likely to affect their functional activity, especially the interaction with specific targets. Therefore, our study represents a step forward in the comprehension of the mechanisms leading to AMD onset and progression, which certainly include the involvement of epigenetic modifications.
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页数:11
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共 42 条
  • [1] Predicting effective microRNA target sites in mammalian mRNAs
    Agarwal, Vikram
    Bell, George W.
    Nam, Jin-Wu
    Bartel, David P.
    [J]. ELIFE, 2015, 4
  • [2] The Impact of the Human Genome Project on Complex Disease
    Bailey, Jessica N. Cooke
    Pericak-Vance, Margaret A.
    Haines, Jonathan L.
    [J]. GENES, 2014, 5 (03): : 518 - 535
  • [3] Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites
    Betel, Doron
    Koppal, Anjali
    Agius, Phaedra
    Sander, Chris
    Leslie, Christina
    [J]. GENOME BIOLOGY, 2010, 11 (08):
  • [4] PolymiRTS Database 3.0: linking polymorphisms in microRNAs and their target sites with human diseases and biological pathways
    Bhattacharya, Anindya
    Ziebarth, Jesse D.
    Cui, Yan
    [J]. NUCLEIC ACIDS RESEARCH, 2014, 42 (D1) : D86 - D91
  • [5] MicroRNAs miR-146a/b negatively modulate the senescence associated inflammatory mediators IL-6 and IL-8
    Bhaumik, Dipa
    Scott, Gary K.
    Schokrpur, Shiruyeh
    Patil, Christopher K.
    Orjalo, Arturo V.
    Rodier, Francis
    Lithgow, Gordon J.
    Campisi, Judith
    [J]. AGING-US, 2009, 1 (04): : 402 - 411
  • [6] Assessing individual risk for AMD with genetic counseling, family history, and genetic testing
    Cascella, R.
    Strafella, C.
    Longo, G.
    Manzo, L.
    Ragazzo, M.
    De Felici, C.
    Gambardella, S.
    Marsella, L. T.
    Novelli, G.
    Borgiani, P.
    Sangiuolo, F.
    Cusumano, A.
    Ricci, F.
    Giardina, E.
    [J]. EYE, 2018, 32 (02) : 446 - 450
  • [7] Towards the application of precision medicine in Age-Related Macular Degeneration
    Cascella, Raffaella
    Strafella, Claudia
    Caputo, Valerio
    Errichiello, Valeria
    Zampatti, Stefania
    Milano, Filippo
    Potenza, Saverio
    Mauriello, Silvestro
    Novelli, Giuseppe
    Ricci, Federico
    Cusumano, Andrea
    Giardina, Emiliano
    [J]. PROGRESS IN RETINAL AND EYE RESEARCH, 2018, 63 : 132 - 146
  • [8] Cascella Raffaella, 2018, Oncotarget, V9, P7812, DOI 10.18632/oncotarget.23241
  • [9] The Genetics and the Genomics of Primary Congenital Glaucoma
    Cascella, Raffaella
    Strafella, Claudia
    Germani, Chiara
    Novelli, Giuseppe
    Ricci, Federico
    Zampatti, Stefania
    Giardina, Emiliano
    [J]. BIOMED RESEARCH INTERNATIONAL, 2015, 2015
  • [10] Chakraborti S., 2017, PROTEASES PHYSL PATH, P325