تالیفات

 

Association analysisofRAC1sin- gle nucleotidepolymorphismswith ulcerativecolitis

مولف: Mohammad Tahera Nasser EbrahimiDaryania Mona Hedayatb, c Mohammad Eslamiana

خلاصه: number ofpossiblecandidategeneshavebeenidentifiedto play acausativeroleinconferringageneticsusceptibilityto UC, resultinginimmunedysregulation.Recently,Muiseetal. reported anovelgeneticassociationbetweenRAC1withUC, a findingsupportedbyhumangeneticandfunctionalstud- ies andanimalmodelsofcolitis [3]. Administrationofthe RAC1 inhibitorNSC23766,aswellasconditionaldisruption of RAC1 [3], decreasedDSS-inducedneutrophilrecruitment and tissuedamageinthecolon.InhibitionofRAC1wasshown to abolishCXCchemokine-inducedneutrophilchemotaxis and up-regulationofMac-1invitro.Inadditiontoitsessen- tial roleinmodulatingimmuneandinflammatoryresponses, RAC1 playsanessentialroleinwoundhealingandepithe- lial celladhesion/migration/differentiation,whichinvolves Rho GTPase-mediatedcytoskeletonremodelinganddisso- lution andreassemblyofcellularjunctions [4]. Moreover, inflammation- andpathogen-inducedRAC1inactivationpro- motes apoptosisandcontributestomicrobialinfectionand barrier dysfunction. In thepresentstudy,three RAC1 gene variants,previously reported toconfersusceptibilitytoUC [3], werestudies in anIranianpatientpopulation.Ourresultsindicatedthat the allelicfrequenciesoftheseSNPswerenotsignifican- tly differentinUCpatientscomparedtocontrols,which was similartowhatwepreviouslyreportedinpatientswith CD [13]. Thiscanbeinpartexplainedbyheterogeneityof the studiedpopulations,suggestingaroleforepigenetic factors inthecomplexinterplaybetweengenesandenvi- ronment amongdifferentethnicpopulations.Italsoshould be emphasizedthatUCisacomplexdisease,inwhichmul- tiple factorscanaffectdiseasebehaviororseverity.Thus, different studydesigns,controlpopulations,andincomplete phenotype descriptioncouldpotentiallyresultindifferent outcomes. GivenitshigherprevalenceinEuropeandNorth America comparedtotheMiddleEasternregions,itcouldbe hypothesized that RAC1 gene variantsmightbeassociated with UCamongpatientsofEuropeanancestry,althoughit needs furtherinvestigations. In conclusion,ourstudydidnotshowanyassociation between thestudiedRAC1SNPsandUCinIranianpatients, similar towhatwefoundinCD.WhetherRAC1,thoughnota predictive geneticbiomarkerbasedontheassessedSNPsin the presentstudy,isamajorplayerinthepathogenesisof UC inourpatientpopulationneedsfurtherinvestigations. Considering ethnicitydifferencesstudyingimmunemodu- lating genesindifferentpopulationswouldshedlightonthe molecular pathogenesisofUC.Thiswilllaythefoundation for improvedpersonalizedmedicineinUCbasedonpharma- cogenetic approachesandtargetedgenetherapy.Further studies ondifferentpopulationswithlargersamplesizes are requiredtoidentifytheexactroleofRAC1andother contributing genesinUC. سال انتشار: 2017
 

RAC1 single nucleotide polymor-phisms in Crohn’s disease

Authers: Mohammad TaheraNasser Ebrahimi DaryaniaMona HedayatbMohammad EslamianaElham Farhadic, dMahdi MahmoudieSamira ShirzadfMohammd Kazem Nouri TaromlouaMeghedi ChaharmahaligMohammad Hossein NicknamcMohammad BashashatihNima

Abstract: diseaseRac1 is a regulator for cellular motility, proliferation andtransformation. A recent showed that mutations of RAC1gene are associated with higher risk of inflammatory boweldisease (IBD). These mutations increase the expression ofRac1 protein and intriguingly, loss of Rac1 expression resultsin protection from colitis [1,2].Thus we conducted a case-control study on 67 patientswith Crohn’s disease (CD) and 78 healthy individuals toidentify whether there is any association between CD andsingle nucleotide polymorphisms (SNPs) ... سال انتشار: 2014
 

ARTICLEInterleukin-23 receptor single nucleotidepolymorphisms in ulcerative colitis. A studyin Iranian populations

Authers: Nasser Ebrahimi Daryania, Farnaz Najmi Varzanehb, Mona Hedayatc, Mohammad Tahera, Elham Farhadia, d, Mahdi Mahmoudie, Mohammad Hossein Nicknamb, Mohammad Bashashatif, Nima Rezaeib,

Abstract: Background/objective: Genetic factors seem to play an important role in the pathogenesis ofulcerative colitis (UC). Genome wide association studies showed a highly significant associationbetween interleukin 23 receptor (IL23R) single nucleotide polymorphisms (SNPs) and Crohn’sdisease; however, there are contrary results regarding the disease-modifying effects of IL23Rvariants in UC. This study was performed in a group of patients with UC to test the possible roleof IL23R SNPs in conferring susceptibility or protection ... سال انتشار: 2014