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Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

Riboflavin and Histidine Metabolisms Are Two Key Pathways Related to the Clinically Isolated Syndrome (CIS): A WGCNA-based In silico Analysis

Author(s): Parvaneh Tavakoli Afshar, Zohreh Taherian, Roya Bakhtiyari, Farzaneh Rami, Masoud Etemadifar and Mansoor Salehi*

Volume 20, Issue 1, 2023

Published on: 31 May, 2023

Page: [57 - 71] Pages: 15

DOI: 10.2174/1875692120666230504114225

Price: $65

Abstract

Background: As an inflammatory disorder, Multiple Sclerosis (MS) causes demyelination, as well as axonal and neuronal injury in the central nervous system (CNS). Several clinical signs may be the indicators of MS among which, Clinically Isolated Syndrome (CIS) is the first symptom caused by the inflammation and demyelination of CNS. CIS is characterized by symptoms such as optic neuritis, brain stem or cerebellar syndrome, spinal cord syndrome, or sometimes cerebral hemispheric dysfunction.

Objective: So far, metabolic pathways involved in the development of CIS are not fully understood. Therefore, in this study, weighted gene co-expression network analysis (WGCNA) has been used to identify differentially expressed genes in CIS disease and the main pathways associated with it.

Methods: We grouped differentially expressed genes along with the functionally related genes into large modules to obtain their direct and indirect relationships.

Results: The results have identified two new pathways associated with CIS, including riboflavin and histidine metabolism-involved pathways.

Conclusion: Riboflavin and histidine metabolism-involved pathways may be considered potential therapeutic goals for CIS management in the future.

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[1]
Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol 2012; 11(2): 157-69.
[http://dx.doi.org/10.1016/S1474-4422(11)70274-5] [PMID: 22265211]
[2]
Grzegorski T, Losy J. What do we currently know about the clinically isolated syndrome suggestive of multiple sclerosis? An update. Rev Neurosci 2020; 31(3): 335-49.
[http://dx.doi.org/10.1515/revneuro-2019-0084] [PMID: 31811811]
[3]
Young J, Quinn S, Hurrell M, Taylor B. Clinically isolated acute transverse myelitis: Prognostic features and incidence. Mult Scler 2009; 15(11): 1295-302.
[http://dx.doi.org/10.1177/1352458509345906] [PMID: 19812117]
[4]
O’Riordan J, Thompson AJ, Kingsley DP, et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain 1998; 121(3): 495-503.
[http://dx.doi.org/10.1093/brain/121.3.495] [PMID: 9549525]
[5]
Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: Natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol 2005; 4(5): 281-8.
[http://dx.doi.org/10.1016/S1474-4422(05)70071-5] [PMID: 15847841]
[6]
Efendi H. Clinically isolated syndromes: Clinical characteristics, differential diagnosis, and management. Noro Psikiyatri Arsivi 2016; 52 (Suppl. 1): 1-11.
[http://dx.doi.org/10.5152/npa.2015.12608] [PMID: 28360754]
[7]
Group ONS. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol 2008; 65(6): 727-32.
[PMID: 18541792]
[8]
Camara-Lemarroy CR, Silva C, Metz LM, et al. Multimodal peripheral fluid biomarker analysis in clinically isolated syndrome and early multiple sclerosis. Mult Scler Relat Disord 2021; 50: 102809.
[http://dx.doi.org/10.1016/j.msard.2021.102809] [PMID: 33581614]
[9]
Marcus JF, Waubant EL. Updates on clinically isolated syndrome and diagnostic criteria for multiple sclerosis. Neurohospitalist 2013; 3(2): 65-80.
[http://dx.doi.org/10.1177/1941874412457183] [PMID: 23983889]
[10]
Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity 2013; 38(4): 633-43.
[http://dx.doi.org/10.1016/j.immuni.2013.04.005] [PMID: 23601682]
[11]
Geiger R, Rieckmann JC, Wolf T, et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 2016; 167(3): 829-42.
[http://dx.doi.org/10.1016/j.cell.2016.09.031]
[12]
Mándi Y, Vécsei L. The kynurenine system and immunoregulation. J Neural Transm 2012; 119(2): 197-209.
[http://dx.doi.org/10.1007/s00702-011-0681-y] [PMID: 21744051]
[13]
Grohmann U, Mondanelli G, Belladonna ML, et al. Amino-acid sensing and degrading pathways in immune regulation. Cytokine Growth Factor Rev 2017; 35: 37-45.
[http://dx.doi.org/10.1016/j.cytogfr.2017.05.004] [PMID: 28545736]
[14]
Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 2005; 4(1): e17.
[http://dx.doi.org/10.2202/1544-6115.1128] [PMID: 16646834]
[15]
Langfelder P, Horvath S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics 2008; 9(1): 559.
[http://dx.doi.org/10.1186/1471-2105-9-559] [PMID: 19114008]
[16]
Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: Archive for functional genomics data sets-update. Nucleic Acids Res 2013; 41: D991-5.
[PMID: 23193258]
[17]
Corvol JC, Pelletier D, Henry RG, et al. Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proc Natl Acad Sci USA 2008; 105(33): 11839-44.
[http://dx.doi.org/10.1073/pnas.0805065105] [PMID: 18689680]
[18]
Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43(7): e47-7.
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[19]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13(11): 2498-504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[20]
Consortium GO. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res 2019; 47(D1): D330-8.
[http://dx.doi.org/10.1093/nar/gky1055] [PMID: 30395331]
[21]
Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28(1): 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]
[22]
Tremlett H, Zhao Y, Rieckmann P, Hutchinson M. New perspectives in the natural history of multiple sclerosis. Neurology 2010; 74(24): 2004-15.
[http://dx.doi.org/10.1212/WNL.0b013e3181e3973f] [PMID: 20548045]
[23]
Hou Y, Jia Y, Hou J. Natural course of clinically isolated syndrome: A longitudinal analysis using a Markov model. Sci Rep 2018; 8(1): 10857.
[http://dx.doi.org/10.1038/s41598-018-29206-y] [PMID: 30022111]
[24]
Makshakov G, Nazarov V, Kochetova O, Surkova E, Lapin S, Evdoshenko E. Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis. PLoS One 2015; 10(11): e0143375.
[http://dx.doi.org/10.1371/journal.pone.0143375] [PMID: 26606531]
[25]
Nagtegaal GJA, Pohl C, Wattjes MP, et al. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome. Mult Scler 2014; 20(2): 234-42.
[http://dx.doi.org/10.1177/1352458513494491] [PMID: 23842212]
[26]
Udyavar AR, Hoeksema MD, Clark JE, et al. Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer. BMC Syst Biol 2013; 7 (Suppl. 5): S1.
[http://dx.doi.org/10.1186/1752-0509-7-S5-S1] [PMID: 24564859]
[27]
Yang Y, Han L, Yuan Y, Li J, Hei N, Liang H. Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types. Nat Commun 2014; 5(1): 3231.
[http://dx.doi.org/10.1038/ncomms4231] [PMID: 24488081]
[28]
Liu J, Jing L, Tu X. Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease. BMC Cardiovasc Disord 2016; 16(1): 54.
[http://dx.doi.org/10.1186/s12872-016-0217-3] [PMID: 26944061]
[29]
Malki K, Tosto MG, Jumabhoy I, et al. Integrative mouse and human mRNA studies using WGCNA nominates novel candidate genes involved in the pathogenesis of major depressive disorder. Pharmacogenomics 2013; 14(16): 1979-90.
[http://dx.doi.org/10.2217/pgs.13.154] [PMID: 24279853]
[30]
Bakhtiarizadeh MR, Hosseinpour B, Shahhoseini M, Korte A, Gifani P. Weighted gene co-expression network analysis of endometriosis and identification of functional modules associated with its main hallmarks. Front Genet 2018; 9: 453.
[http://dx.doi.org/10.3389/fgene.2018.00453] [PMID: 30369943]
[31]
Thakur K, Tomar SK, Singh AK, Mandal S, Arora S. Riboflavin and health: A review of recent human research. Crit Rev Food Sci Nutr 2017; 57(17): 3650-60.
[http://dx.doi.org/10.1080/10408398.2016.1145104] [PMID: 27029320]
[32]
Cai Z, Finnie JW, Blumbergs PC, Manavis J, Ghabriel MN, Thompson PD. Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy. Exp Neurol 2006; 198(1): 65-71.
[http://dx.doi.org/10.1016/j.expneurol.2005.10.028] [PMID: 16336963]
[33]
Cai Z, Finnie JW, Blumbergs PC. Avian riboflavin deficiency: An acquired tomaculous neuropathy. Vet Pathol 2006; 43(5): 780-1.
[http://dx.doi.org/10.1354/vp.43-5-780] [PMID: 16966461]
[34]
Naghashpour M, Majdinasab N, Shakerinejad G, et al. Riboflavin supplementation to patients with multiple sclerosis does not improve disability status nor is riboflavin supplementation correlated to homocysteine. Int J Vitam Nutr Res 2013; 83(5): 281-90.
[PMID: 25305223]
[35]
Ogunleye AJ, Odutuga AA. The effect of riboflavin deficiency on cerebrum and cerebellum of developing rat brain. J Nutr Sci Vitaminol 1989; 35(3): 193-7.
[http://dx.doi.org/10.3177/jnsv.35.193] [PMID: 2760691]
[36]
Naghashpour M, Jafarirad S, Amani R, Sarkaki A, Saedisomeolia A. Update on riboflavin and multiple sclerosis: A systematic review. Iran J Basic Med Sci 2017; 20(9): 958-66.
[PMID: 29085589]
[37]
Grohmann U, Bronte V. Control of immune response by amino acid metabolism. Immunol Rev 2010; 236(1): 243-64.
[http://dx.doi.org/10.1111/j.1600-065X.2010.00915.x] [PMID: 20636821]
[38]
Mondanelli G, Ugel S, Grohmann U, Bronte V. The immune regulation in cancer by the amino acid metabolizing enzymes ARG and IDO. Curr Opin Pharmacol 2017; 35: 30-9.
[http://dx.doi.org/10.1016/j.coph.2017.05.002] [PMID: 28554057]
[39]
Negrotto L, Correale J. Amino acid catabolism in multiple sclerosis affects immune homeostasis. J Immunol 2017; 198(5): 1900-9.
[http://dx.doi.org/10.4049/jimmunol.1601139] [PMID: 28130499]
[40]
Mondanelli G, Iacono A, Carvalho A, et al. Amino acid metabolism as drug target in autoimmune diseases. Autoimmun Rev 2019; 18(4): 334-48.
[http://dx.doi.org/10.1016/j.autrev.2019.02.004] [PMID: 30797943]
[41]
Loy BD, Fling BW, Sage KM, Spain RI, Horak FB. Serum histidine is lower in fatigued women with multiple sclerosis. Fatigue 2019; 7(2): 69-80.
[http://dx.doi.org/10.1080/21641846.2019.1611786] [PMID: 32440368]
[42]
Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev 2008; 88(3): 1183-241.
[http://dx.doi.org/10.1152/physrev.00043.2007] [PMID: 18626069]
[43]
Sasahara I, Fujimura N, Nozawa Y, Furuhata Y, Sato H. The effect of histidine on mental fatigue and cognitive performance in subjects with high fatigue and sleep disruption scores. Physiol Behav 2015; 147: 238-44.
[http://dx.doi.org/10.1016/j.physbeh.2015.04.042] [PMID: 25921948]
[44]
Teuscher C, Subramanian M, Noubade R, et al. Central histamine H 3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. Proc Natl Acad Sci USA 2007; 104(24): 10146-51.
[http://dx.doi.org/10.1073/pnas.0702291104] [PMID: 17548817]
[45]
Musio S, Gallo B, Scabeni S, et al. A key regulatory role for histamine in experimental autoimmune encephalomyelitis: Disease exacerbation in histidine decarboxylase-deficient mice. J Immunol 2006; 176(1): 17-26.
[http://dx.doi.org/10.4049/jimmunol.176.1.17] [PMID: 16365391]
[46]
Gandhi KS, McKay FC, Cox M, et al. The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet 2010; 19(11): 2134-43.
[http://dx.doi.org/10.1093/hmg/ddq090] [PMID: 20190274]

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