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Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes
CHAUVET-GÉLINIER, J.-C., et al.
Abstract
Type A personality has been associated with increased survival in people with type 1 diabetes (T1D). Systemic low-grade inflammation may play a critical role, as suggested in recent reports, although the links between the inflammatory circulating transcriptome and Type A remain unknown. This prompted our exploration of the potential associations between Type A personality and c-Fos gene expression, a candidate gene closely linked to inflammatory processes, in T1D.
CHAUVET-GÉLINIER, J.-C., et al . Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes. Diabetes & Metabolism , 2019, vol. 45, no. 6, p. 582-585
DOI : 10.1016/j.diabet.2018.11.005 PMID : 30476653
Available at:
http://archive-ouverte.unige.ch/unige:145017
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1 / 1
Short Report
Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes
J.-C. Chauvet-Ge´linier
a,d, A.-L. Mosca-Boidron
h, C. Lemogne
e,f,g, S. Ragot
h, N. Forestier
a, D. Callegarin
h, C. Allard
a, A. Rebaı¨
a, B. Bouillet
c,d, E. Ponavoy
a, I. Simoneau
c,d, J.-M. Petit
c,d, G. Bondolfi
i, P. Callier
h, B. Trojak
a, B. Bonin
a,b, B. Verge`s
c,d,*
aPsychiatryunit,departmentofneurosciences,universityhospital,CHUdeLeBocage,BaˆtimentMarion,14,rueGaffarel,21000Dijon,France
bLaboratoiredepsychopathologieetdepsychologieme´dicale(IFR100),universite´ deBourgogne-Franche-Comte´,21000Bourgogne-Franche-Comte´France
cDepartmentofendocrinologyandmetabolicdiseases,universityhospitalCHUdeLeBocage,2,boulevardMare´chaldeLattredeTassigny,21000Dijon,France
dInsermLNC-UMR1231,21000Dijon,France
eUniversite´ ParisDescartes,SorbonneParisCite´,faculte´ deme´decine,75006Paris,France
fAP–HP,hoˆpitauxuniversitairesParisOuest,servicedepsychiatrieetd’addictologiedel’adulteetdusujetaˆge´,75015Paris,France
gInserm,centreforpsychiatryandneuroscience,U894,21000Paris,France
hLaboratoiredege´ne´tiquechromosomiqueetmole´culaire,plateformedebiologiehospitalo-universitaire,CHUdeleBocage,Dijon,France
iServicedepsychiatriedeliaisonetd’interventiondecrise,hoˆpitauxuniversitairesdeGene`ve,Geneva,Switzerland
Introduction
TheTypeApersonality,whichischaracterizedbytimeurgency, strongdrive,andneedforachievementandcompetitiveness,has been suggested to influence health outcomes [1,2]. Although earlier reports mentioned that Type A was associated with a
greater risk of developing coronary heart disease, subsequent studies dismissed the link and instead focused attention on hostility asthe ‘toxic’ component, as otherType A personality components,suchascompetitiveness,couldhaveapositiveimpact [1,2].Infact,intype1diabetes(T1D),theTypeApersonalityhas beenassociatedwithlowercardiovascularandall-causemortality [3].
Amongthebiological mechanisms potentiallymediating the association between Type A personality and clinical outcomes, systemic low-grade inflammation may play a critical role, as suggestedinrecentreportswhereinTypeAwasassociatedwith ARTICLE INFO
Articlehistory:
Received16August2018
Receivedinrevisedform13November2018 Accepted14November2018
Availableonline23November2018
Keywords:
c-Fos
Competitiveness Diabetes Inflammation Personality TypeA
ABSTRACT
Aim.– TypeApersonalityhasbeenassociatedwithincreasedsurvivalinpeoplewithtype1diabetes (T1D).Systemiclow-gradeinflammationmayplayacriticalrole,assuggestedinrecentreports,although thelinksbetween theinflammatorycirculating transcriptome and TypeA remain unknown.This promptedourexplorationofthepotentialassociationsbetween TypeApersonalityandc-Fosgene expression,acandidategenecloselylinkedtoinflammatoryprocesses,inT1D.
Methods.–TypeApersonalitywasassessedbyBortnerquestionnaireinpatientswithT1D,andtwo subscales–‘speed’and‘competitiveness’–wereusedtomeasurethesespecificdimensionsofTypeA.
Expressionof thec-Fos gene was assessed bya quantitativereal-time polymerase chainreaction technique.
Results.– Thispilotstudyincluded20menwithT1D.Multivariableanalysesshowedanindependent inverseassociationbetweenTypeAcompetitivenessscoreandc-Fosexpression,whilearegression modeladjustedforage,bodymassindexandHbA1clevelsrevealedasignificantinverserelationship betweenc-FostranscriptsandTypeAcompetitiveness(P=0.003).
Conclusion.–ThisstrongassociationbetweenTypeAcompetitivenessandreducedc-Fosexpressionis inline with recent data suggesting apsychobiological influenceofthe TypeA profilein T1Dvia inflammatorypathways.
C2018TheAuthor(s).PublishedbyElsevierMassonSAS.ThisisanopenaccessarticleundertheCCBY- NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
* Correspondingauthorat:Departmentofendocrinologyandmetabolicdiseases, universityhospitalCHUdeLeBocage,InsermLNC-UMR,2,boulevardMare´chalde LattredeTassigny,21000Dijon,France.
E-mailaddress:bruno.verges@chu-dijon.fr(B.Verge`s).
Availableonlineat
ScienceDirect
www.sciencedirect.com
https://doi.org/10.1016/j.diabet.2018.11.005
1262-3636/C2018TheAuthor(s).PublishedbyElsevierMassonSAS.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by- nc-nd/4.0/).
reduced plasma C-reactive protein (CRP) in patients with T1D [1]. To date, however, the links between the inflammatory circulatingtranscriptomeandTypeApersonalityhaveremained unknownindiabetes.Morespecifically,theFinkel–Biskis–Jinkins osteosarcomavirus(c-Fos)genehasbeenevenmorecloselylinked toinflammatoryprocessesincirculatingbloodcells[4]thanisthe CRP marker, although its links to psychobiological phenomena haveremainedunexploredindiabetes.Indeed,thispromptedthe presentpilotstudyof20patientswithT1Dtolookforapotential associationbetweenTypeApersonalityandc-Fosgeneexpression.
Methods
Participants
Thestudypopulationconsistedofmenaged35–45yearswith T1D,allofwhomhadbeenseenasoutpatientsintheEndocrinol- ogy and Metabolic Diseases Department of Dijon University Hospital.
Ethics
The study (NCT02080741) received approval from thelocal ethicscommittee.Priortothepatients’interviewsandmeasure- ments,theinterviewer described theaim ofthe study toeach participantandobtainedtheirfullwrittenconsent.
Clinicalandbiologicalmeasurements
MaleparticipantswithT1DwererecruitedattheEndocrinology andMetabolicDiseasesDepartmentofDijonUniversityHospital.
All underwent standardized clinical examinations, and their clinicaldatawererecordedbydirectinterviewandbyareview oftheirmedicalrecords.Patientsparticipatinginintensephysical activitywerenotincludedinthestudy.
Foreachrecruitedparticipant,bloodwasdrawnat0800hin the morning in a fasting state to assess levels of glycated haemoglobin (HbA1c) and c-Fos gene expression. All biological parameters were determined at the Dijon University Hospital laboratory. HbA1c was measured by ion-exchange high-perfor- mance liquid chromatography (HPLC; Bio-Rad Laboratories, Hercules,CA,USA)aspreviouslydescribed[1].Leucocyteribonu- cleicacid(RNA)wasextractedfromperipheralbloodsamples.
Levelsoftranscriptsinbloodleucocytesweremeasuredbythe quantitative real-time polymerase chain reaction (qRT-PCR) method,asdescribedpreviouslyindetail [5].Purityandquality wereassessedbyabsorbanceatultraviolet(UV)wavelengthsof 260nmand280nm,anda260/280ratio>1.8wasrequiredfor furtheranalysis.ThequalityofRNA,computedastheRNAintegrity number (RIN), was assessed with a 2100 Bioanalyzer (Agilent Technologies,SantaClara,CA,USA)usingRNA6000NanoChips (Agilent Technologies). For quantification of transcripts, mean cyclethreshold(Ct) valuesof targetand referencegenesin the differentgroupswereanalyzedandcomparedusingtherelative expressionsoftwaretool (REST;2008V2.0.7), whichprovides a normalized expression ratio for each gene and calculates the significanceofdifferencesingeneexpressionusingarandomiza- tionalgorithm.
Psychologicalmeasurements
TypeApersonality:speedandcompetitivenessdimensions
TomeasureTypeA,theBortnerTypeARatingScale(BTRS)was used[6].Thisscalewastranslatedand validatedfortheFrench population against the Friedman and Rosenman structured
interviewforassessingTypeA[7],andfoundtohaveanobserved agreementof71.5% [8].TheBTRSisrecognizedforitsabilityto assess time urgency and impatience, competitiveness and job involvement withoutmeasuringhostility[9].Itis worthnoting thatanassociationbetweenTypeAandlowerratesofmortalityin patientswithdiabetes[3]wasfoundwiththeBTRS.Accordingto Edwardsetal.[10],twosubscales–nineitemsfor‘speed’(never late, rushed, impatient,goesall out,does lotsat once,forceful, wants job recognition, fast,hides feelings) and three items for
‘competitiveness’ (competitive, hard-driving, ambitious)– were usedtoassessthesespecificdimensionsoftheTypeApersonality.
Statisticalanalysis
Descriptivedataforcontinuousvariableshavebeenreportedas meansSD (standarddeviation). As relianceon a binary cut-off pointcouldproducespuriousresults,theBTRSscorewasconsidereda continuousvariable.Univariatecorrelationanalysiswasperformed bycalculationofPearson’scoefficient.Thegeneexpressionvariable wasthemeanCtratioofc-Fos/glyceraldehyde-3-phosphatedehy- drogenase (GAPDH). Multivariable analyses were performed by multiplelinearregressiontodeterminetheindependentassociation betweenpersonalitytraitsandc-Fosgeneexpression,thedependent variable, while taking into account the potentially confounding factorsofage,bodymassindex(BMI),diabetesdurationandHbA1c
levels.
A two-tailed probability (P) level of 0.05 was accepted as statistically significant. All statistical analyses were performed usingSPSSsoftware(IBMCorp.,Armonk,NY,USA).
Results
Generalcharacteristics
This pilot study included 20 European men ages 35 to 45 (40.863.62)years,andfollowedthembetween2015and2017.All had been diagnosed with T1D (mean duration of disease:
22.919.11years; meanHbA1c levels:7.311.29%; mean BMI:
28.875.62kg/m2). As fordiabetes complications, only sixmen (30%) hadretinopathy; none had coronaropathy, nephropathy or neuropathy; all were non-smokers; and no alcohol misuse was observed. In addition, their mean total BTRS score was 200.0043.57, their mean speed Dimension Score was 139.2735.22 and their mean competitiveness dimension score was37.3614.05.Themeanc-FostranscriptCtwas0.910.04.
Associationbetweenc-FosgeneexpressionandTypeApersonality BivariateanalysesindicatedthatTypeAcompetitivenesstraits correlatedwithc-Fosexpression(r= 0.708,P=0.001;Fig.1)and HbA1clevels(r= 0.544,P=0.011),butnotwitheitherageorBMI.
On the other hand, Type A speed traits correlated with BMI (r=0.465,P=0.019),butnotwithage,c-FosorHbA1clevels.In multiple regression analyses, c-Fos was significantly associated with competitiveness independently of age, BMI and HbA1c
(P=0.003).
Discussion
Thepresentstudy,thefirsttoexaminetherelationshipbetween TypeApersonalityandc-FosgeneexpressioninpatientswithT1D, has identified an inverse association between the Type A competitiveness dimension and c-Fos expression.Fickley et al.
[3] revealedthat cardiacand all-causemortalitywerelower in individualswithTypeApersonalityandT1D.Whilethereasonsfor J.-C.Chauvet-Ge´linieretal./Diabetes&Metabolism45(2019)582–585 583
thisreducedmortalityarestillunknown,ourpresentdatasuggest thatitmightbemediatedbyinflammatoryprocesses,whichisin line withrecent datashowingan inverserelationship between TypeA and plasma CRP levels[1]. As TypeA competitiveness encompassesboththe‘proactive’and‘goal-striving’components of the Type A profile that are similar to the higher-order conscientiousnesspersonalitydimension[11],ourresultsarealso consistentwithanassociationofconscientiousnesswithreduced inflammation[12].Inaddition,severalreportshavesuggestedthat being highly reactive (as are people scoring high on Type A competitiveness)inachallengingenvironment(suchasT1D)could bebeneficial in terms of producing more effectivebehavioural copingstrategies[13].Indeed,peoplewithhighlevelsofTypeA competitiveness, who are mainly ‘goal-oriented’ and conscien- tious,maybemorelikelytodisplayprotectivehealthbehaviours, suchasengaginginphysicalactivity[3].
Consistent with this view, Type A has been shown to be associated with more problem-focused coping strategies [14], including searching for appropriate medical treatments [7], adherencetoscreening[15]and agreatersenseof self-efficacy [16], which is associated with better adherence to diabetes regimens[17].Overall,itcouldbesuggestedthatindividualswith highlevelsofcompetitivenessmaydisplaymoreadaptivehealth behavioursin the faceof diabetes, thuseventually resulting in betterclinicaloutcomes.Competitivenesshasalsobeenassociated withlongertelomerelengths[13],lowerplasmaCRPlevels[1]and, inourpresentstudy,reducedc-Fosgeneexpression.Allthesedata suggestapotentiallydirectlinkbetweenTypeAcompetitiveness andbiologyand,moreprecisely,inflammatorymarkers.
Inaddition,bivariateanalysishasrevealedasignificantinverse correlation between Type A competitiveness and glycaemic control,asmeasuredbyHbA1clevels.Aspreviouslydiscussed,it ispossiblethatthosewithstrongcompetitivenesstraitsmayhave better adaptive behaviours and good medication adherence.
However,controversialliteraturealsosuggeststhattherelation- shipbetween TypeA and betterclinical outcomesmay notbe supportedbyanindependentlinkbetweenTypeApersonalityand HbA1clevels[3,18,19].
The TypeA speeddimension was positivelyassociated with BMI, which appears to be in agreement with previous studies showinganassociationbetweenimpatienceormotorimpulsive- nessandincreasedBMI[20,21].Nevertheless,itisnoteworthythat theseresultswereobtainedinpeoplewithoutdiabetes.Moreover,
thepresentstudy,performed inpatientswithT1D,revealedno influenceof BMIon thesignificantassociationbetweenType A competitivenessandc-Fosexpression.Thus,itmaybespeculated thatanegativeeffectoftheTypeAspeeddimensiononfoodintake might be counterbalanced by TypeA competitiveness traits in patientswithT1D.
In this pilotstudy of 20 patients withT1D, there are some limitations mostly due to its cross-sectional and observational design whereby associations, but never causal relationships, betweenthecompetitivenesspersonalitytraitsandc-Fosexpres- sionhave beendemonstrated. Indeed,despitethe factthat the literatureexhaustivelysupportstop-downeffectsofpsychological features on the inflammatory process, some reports have consistently highlightedthebottom-upimpactof inflammation onthebrainandbehaviour[22].Therefore,inT1D,inflammation couldbealteringpersonalitytraitsbyreducingboththephysical andcognitivecapacitytodealwithadversity,therebyalteringType Acompetitiveness.Inthisregard,ourstudydesignwasnotableto teaseout the possiblereciprocal relationships between Type A competitiveness and inflammatorypathways. Moreover, certain clinicalandbiologicaldata,suchasdepression,physicalactivity and CRP plasma levels, were not assessed in this pilot study, whereas it cannot beexcluded that those unmeasured factors, commonly associated with systemic inflammation, may have confoundedthelinkbetweencompetitivenessandc-Fosexpres- sion[23–25].
Nevertheless, it seems important to note that all patients enrolled in ourstudywerenon-smokers,thereby eliminatinga majorconfoundingfactorshowntobethestrongestpredictorofc- Fostranscriptlevels[26].Inaddition,T1Dpatientsparticipatingin intensephysicalactivitywereexcludedfromourstudy.Finally, despitesomelimitations,ourfindingshavedemonstratedastrong associationbetween TypeAcompetitiveness andreduced c-Fos expression,whichisinlinewithrecentdatalinkingTypeAand low-gradeinflammationinT1D[1].
Conclusion
Althoughthemechanism(s)underlyingtherelationshipbetween TypeApersonalityandinflammatoryprocessesremainunclear,the presentstudyhasidentifiedsomepotentialgenomiclinksbetween TypeApersonalityandc-FosexpressioninT1D.Furtherlongitudinal Fig.1.Correlationbetweenlevelsofc-Fosgeneexpression(r= 0.708,P=0.001)andTypeAcompetitivenessscore(Bortnerquestionnaire).
studiesarenowneededtoexaminethepotentialroleoflow-grade inflammationinmediatingtheassociationofTypeAwithclinical outcomesindiabetes,andtoclarifythemechanismsthatmaylink personalityandinflammation.
Funding
ThisworkwassupportedbyagrantfromtheFrenchEasternInterregionalGroupof ClinicalResearchandInnovation(GIRCIEst)withintheframeworkofaClinical ResearchProtocol (Appel a` Projet‘‘Jeunes Chercheurs’’2013) promoted byJ.C.
Chauvet-Gelinier.
Disclosureofinterest
Theauthorsdeclarethattheyhavenocompetinginterest.
Acknowledgments
The authors are grateful for the contributions of all study participants, and for the work and dedication of the entire endocrinologydepartmentstaff.WealsothankVe´roniqueGrivet, Ce´cile Breuillet and Philippe Loisel for their expert technical assistance.
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