Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-14T15:16:11.778Z Has data issue: false hasContentIssue false
  • English
  • Français

A functional SNP in MIR124-1, a brain expressed miRNA gene, is associated with aggressiveness in a Colombian sample

Published online by Cambridge University Press:  15 April 2020

Y. González-Giraldo ,
A. Camargo ,
S. López-León ,
A. Adan  and
D.A. Forero
Y. González-Giraldo
Affiliation:
Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia
A. Camargo
Affiliation:
School of Nursing, Universidad de Ciencias Aplicadas y Ambientales UDCA, Bogotá, Colombia
S. López-León
Affiliation:
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
A. Adan
Affiliation:
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain Institute for Brain, Cognition and Behavior (IR3 C), Barcelona, Spain
D.A. Forero*
Affiliation:
Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia
*
*Corresponding author. Tel.: +57 313 2610427. E-mail address:[email protected] (D.A. Forero).
Get access

Abstract

Background:

Interpersonal violence and suicide are among the main causes of mortality and morbidity around the world. In several developing countries, such as Colombia, they are among the first five entities of public health concern. Aggressiveness is an important endophenotype for aggression and suicidal behavior, having a heritability of around 50%. Exploration of classical candidate genes, involved in serotoninergic and dopaminergic neurotransmission, has identified few consistent risk factors for aggressiveness. miRNAs are a novel class of molecules with a growing role in normal neural function and neuropsychiatric disorders; of special interest, miR-124 is a brain-specific miRNA that is key for neuronal plasticity. We evaluated the hypothesis that a functional polymorphism in MIR124-1 gene might be associated with aggressiveness in a Colombian sample.

Methods:

The Spanish adaptation of the refined version of the Aggression Questionnaire and the abbreviated Barratt Impulsiveness Scale were applied to 170 young subjects. The functional SNP in MIR124-1 (rs531564) was genotyped by a TaqMan assay.

Results:

We found a significant association between the MIR124-1 and aggressiveness in our sample, with G/G carriers having lower scores (P = 0.01). This association seemed to be specific for aggressiveness, as it was not significant for impulsiveness.

Conclusions:

We showed for the first time the association of a functional polymorphism in MIR124-1 and aggressiveness. Known targets of miR-124 (such as BDNF and DRD4 genes) could explain the effect of this miRNA on behavior. A future analysis of additional novel functional polymorphisms in other brain expressed miRNAs could be useful for a deeper understanding of aggression in humans.

Keywords

AggressionEndophenotypesLatin AmericancRNAsPsychiatric geneticsViolence
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 4 , June 2015 , pp. 499 - 503
Copyright
Copyright © Elsevier Masson SAS 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Abbreviations: BDNF, brain-derived neurotrophic factor; GABBR2, gamma-aminobutyric acid B receptor 2; DRD4, dopamine receptor D4; SLITRK4, SLIT and NTRKlike family member 4; SNAP23, synaptosomal-associated protein 23 kDa; RGS4, regulator of G-protein signaling 4; VAMP3, vesicle-associated membrane protein 3; ROBO3, roundabout, axon guidance receptor, homolog 3; ASW, African ancestry in Southwest USA; CEU, Northern Europeans from Utah, USA; CHB, Han Chinese in Beijing, China; CHD, Chinese in Denver, USA; CLB, Colombians in Bogotá, Colombia; GIH, Gujarati Indians in Houston, Texas; JPT, Japanese in Tokyo, Japan; LWK, Luhya in Webuye, Kenya; MXL, Mexican ancestry in Los Angeles, USA; MKK, Maasai in Kinyawa, Kenya; TSI, Toscani in Italia; YRI, Yoruba in Ibadan, Nigeria.

References

Alaerts, M, Ceulemans, S, Forero, D, Moens, LN, De Zutter, S, Heyrman, Let al.Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population. Am J Med Genet B Neuropsychiatr Genet 2009;150B:585–592.CrossRefGoogle ScholarPubMed
Anholt, RR, Mackay, TFGenetics of aggression. Annu Rev Genet 2012; 46: 145–164.CrossRefGoogle ScholarPubMed
Bahi, A, Dreyer, JLStriatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption. Eur J Neurosci 2013; 38: 2328–2337.CrossRefGoogle ScholarPubMed
Bahi, A, Chandrasekar, V, Dreyer, JLSelective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats. Psychoneuroendocrinology 2014; 46: 78–87.CrossRefGoogle ScholarPubMed
Benitez, BA, Forero, DA, Arboleda, GH, Granados, LA, Yunis, JJ, Fernandez, Wet al.Exploration of genetic susceptibility factors for Parkinson's disease in a South American sample. J Genet 2010; 89: 229–232.CrossRefGoogle Scholar
Beskow, LM, Burke, W, Merz, JF, Barr, PA, Terry, S, Penchaszadeh, VBet al.Informed consent for population-based research involving genetics. JAMA 2001; 286: 2315–2321.CrossRefGoogle ScholarPubMed
Bryant, FB, Smith, BDRefining the architecture of aggression: a measurement model for the Buss–Perry Aggression Questionnaire. J Res Pers 2001; 35: 138–167.CrossRefGoogle Scholar
Buss, AH, Perry, MThe aggression questionnaire. J Pers Soc Psychol 1992;63:452.CrossRefGoogle ScholarPubMed
Chandrasekar, V, Dreyer, JLmicroRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity. Mol Cell Neurosci 2009; 42: 350–362.CrossRefGoogle ScholarPubMed
El-Kordi, A, Kastner, A, Grube, S, Klugmann, M, Begemann, M, Sperling, Set al.A single gene defect causing claustrophobia. Transl Psychiatry 2013;3:e254.CrossRefGoogle ScholarPubMed
Forero, DA, Arboleda, G, Yunis, JJ, Pardo, R, Arboleda, HAssociation study of polymorphisms in LRP1, tau and 5-HTT genes and Alzheimer's disease in a sample of Colombian patients J Neural Transm 2006; 113: 1253–1262CrossRefGoogle Scholar
Forero, DA, van der Ven, K, Callaerts, P, Del-Favero, JmiRNA genes and the brain: implications for psychiatric disorders. Hum Mutat 2010; 31: 1195–1204CrossRefGoogle ScholarPubMed
Forero, DA, Velez-van-Meerbeke, A, Deshpande, SN, Nicolini, H, Perry, GNeuropsychiatric genetics in developing countries: current challenges. World J Psychiatry 2014; 4: 69–71.CrossRefGoogle ScholarPubMed
Forero, DA, Lopez-Leon, S, Shin, HD, Park, BL, Kim, DJMeta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence. Drug Alcohol Depend 2015; 149: 259–263.CrossRefGoogle ScholarPubMed
Gallardo-Pujol, D, Kramp, U, Garcia-Forero, C, Perez-Ramirez, M, Andres-Pueyo, AAssessing aggressiveness quickly and efficiently: the Spanish adaptation of Aggression Questionnaire-refined version. Eur Psychiatry 2006; 21: 487–494.CrossRefGoogle ScholarPubMed
Gao, FBContext-dependent functions of specific microRNAs in neuronal development. Neural Dev 2010;5:25.CrossRefGoogle ScholarPubMed
Gascon, E, Lynch, K, Ruan, H, Almeida, S, Verheyden, JM, Seeley, WWet al.Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med 2014; 20: 1444–1451.CrossRefGoogle ScholarPubMed
Gong, Y, Wu, CN, Xu, J, Feng, G, Xing, QH, Fu, Wet al.Polymorphisms in microRNA target sites influence susceptibility to schizophrenia by altering the binding of miRNAs to their targets. Eur Neuropsychopharmacol 2013; 23: 1182–1189CrossRefGoogle ScholarPubMed
Herbert, HK, Hyder, AA, Butchart, A, Norton, RGlobal health: injuries and violence. Infect Dis Clin North Am 2011; 25: 653–668. x.CrossRefGoogle ScholarPubMed
Hernandez, HG, Tse, MY, Pang, SC, Arboleda, H, Forero, DAOptimizing methodologies for PCR-based DNA methylation analysis. Biotechniques 2013; 55: 181–197.CrossRefGoogle ScholarPubMed
International HapMap, C, Altshuler, DM, Gibbs, RA, Peltonen, L, Altshuler, DM, Gibbs, RAet al.Integrating common and rare genetic variation in diverse human populations. Nature 2010; 467: 52–58.CrossRefGoogle Scholar
Jensen, KP, Covault, J, Conner, TS, Tennen, H, Kranzler, HR, Furneaux, HMA common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors. Mol Psychiatry 2009; 14: 381–389.CrossRefGoogle ScholarPubMed
Karolchik, D, Barber, GP, Casper, J, Clawson, H, Cline, MS, Diekhans, Met al.The UCSC Genome Browser database: 2014 update. Nucleic Acids Res 2014;42:D764–D770.CrossRefGoogle ScholarPubMed
Kovacs-Nagy, R, Elek, Z, Szekely, A, Nanasi, T, Sasvari-Szekely, M, Ronai, ZAssociation of aggression with a novel microRNA binding site polymorphism in the wolframin gene. Am J Med Genet B Neuropsychiatr Genet 2013;162B:404–412.CrossRefGoogle ScholarPubMed
Liang, Y, Ridzon, D, Wong, L, Chen, CCharacterization of microRNA expression profiles in normal human tissues. BMC Genomics 2007;8:166.CrossRefGoogle ScholarPubMed
Lozano, R, Naghavi, M, Foreman, K, Lim, S, Shibuya, K, Aboyans, Vet al.Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095–2128.CrossRefGoogle ScholarPubMed
Makeyev, EV, Zhang, J, Carrasco, MA, Maniatis, TThe microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007; 27: 435–448CrossRefGoogle ScholarPubMed
Mann, JJ, Arango, VA, Avenevoli, S, Brent, DA, Champagne, FA, Clayton, Pet al.Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry 2009; 65: 556–563.CrossRefGoogle ScholarPubMed
Miles, DR, Carey, GGenetic and environmental architecture of human aggression. J Pers Soc Psychol 1997; 72: 207–217.CrossRefGoogle ScholarPubMed
Morales, LC, Arboleda, G, Rodriguez, Y, Forero, DA, Ramirez, N, Yunis, JJet al.Absence of Lamin A/C gene mutations in four Wiedemann-Rautenstrauch syndrome patients. Am J Med Genet A 2009;149A:2695–2699.CrossRefGoogle ScholarPubMed
Murray, CJ, Lopez, ADMeasuring the global burden of disease. N Engl J Med 2013; 369: 448–457.CrossRefGoogle ScholarPubMed
Murray, CJ, Vos, T, Lozano, R, Naghavi, M, Flaxman, AD, Michaud, Cet al.Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2197–2223.CrossRefGoogle ScholarPubMed
Ojeda, DA, Perea, CS, Nino, CL, Gutierrez, RM, Lopez-Leon, S, Arboleda, Het al.A novel association of two non-synonymous polymorphisms in PER2 and PER3 genes with specific diurnal preference subscales. Neurosci Lett 2013; 553: 52–56CrossRefGoogle ScholarPubMed
Ojeda, DA, Perea, CS, Suarez, A, Nino, CL, Gutierrez, RM, Lopez-Leon, Set al.Common functional polymorphisms in SLC6A4 and COMT genes are associated with circadian phenotypes in a South American sample. Neurol Sci 2014; 35: 41–47CrossRefGoogle Scholar
Ojeda, DA, Lopez-Leon, S, Forero, DAA novel cost-effective assay based on real-time PCR for COMT Val158Met genotyping. Biomarkers 2014; 19: 567–570.CrossRefGoogle ScholarPubMed
Orozco-Cabal, L, Rodriguez, M, Herin, DV, Gempeler, J, Uribe, MValidity and reliability of the abbreviated Barratt Impulsiveness Scale in Spanish (BIS-15S). Rev Colomb Psiquiatr 2010; 39: 93–109.CrossRefGoogle Scholar
Patton, GC, Coffey, C, Sawyer, SM, Viner, RM, Haller, DM, Bose, Ket al.Global patterns of mortality in young people: a systematic analysis of population health data. Lancet 2009; 374: 881–892.CrossRefGoogle ScholarPubMed
Qi, L, Hu, Y, Zhan, Y, Wang, J, Wang, BB, Xia, HFet al.A SNP site in pri-miR-124 changes mature miR-124 expression but no contribution to Alzheimer's disease in a Mongolian population. Neurosci Lett 2012; 515: 1–6CrossRefGoogle Scholar
Sharan, P, Gallo, C, Gureje, O, Lamberte, E, Mari, JJ, Mazzotti, Get al.Mental health research priorities in low- and middle-income countries of Africa, Asia, Latin America and the Caribbean. Br J Psychiatry 2009; 195: 354–363CrossRefGoogle ScholarPubMed
Siever, LJNeurobiology of aggression and violence. Am J Psychiatry 2008; 165: 429–442.CrossRefGoogle ScholarPubMed
Smarr, KL, Keefer, ALMeasures of depression and depressive symptoms: Beck Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Res 2011;63(Suppl. 11):S454–S466.CrossRefGoogle Scholar
Sole, X, Guino, E, Valls, J, Iniesta, R, Moreno, VSNPStats: a web tool for the analysis of association studies. Bioinformatics 2006; 22: 1928–1929CrossRefGoogle ScholarPubMed
Spinella, MNormative data and a short form of the Barratt Impulsiveness Scale. Int J Neurosci 2007; 117: 359–368CrossRefGoogle Scholar
Strazisar, M, Cammaerts, S, van der Ven, K, Forero, DA, Lenaerts, AS, Nordin, Aet al.MIR137 variants identified in psychiatric patients affect synaptogenesis and neuronal transmission gene sets. Mol Psychiatry 2014 10.1038/mp.2014.53 [Epub ahead of print].Google ScholarPubMed
Vassos, E, Collier, DA, Fazel, SSystematic meta-analyses and field synopsis of genetic association studies of violence and aggression. Mol Psychiatry 2014; 19: 471–477CrossRefGoogle ScholarPubMed
Vlachos, IS, Paraskevopoulou, MD, Karagkouni, D, Georgakilas, G, Vergoulis, T, Kanellos, Iet al.DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions. Nucleic Acids Res 2015;43:D153–D159.CrossRefGoogle ScholarPubMed
Yang, L, Zhang, R, Li, M, Wu, X, Wang, J, Huang, Let al.A functional MiR-124 binding-site polymorphism in IQGAP1 affects human cognitive performance. PloS One 2014;9:e107065.CrossRefGoogle ScholarPubMed
Supplementary material: File

González-Giraldo et al. supplementary material

Figure S1

Download González-Giraldo et al. supplementary material(File)
File 16.1 KB
Submit a response

Comments

No Comments have been published for this article.