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Novel Effects of Hormonal Contraceptive Use on the Plasma Proteome 英文参考文献
NovelEffectsofHormonalContraceptiveUseonthe
PlasmaProteome
AndreaR.Josse1.,BibianaGarcia-Bailo1.,KarinaFischer1,2,AhmedEl-Sohemy1*
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 2Institute of Food, Nutrition and Health, Department of
AgricultureandFoodSciences,ETHZurich,Zurich,Switzerland
Abstract
Background:Hormonalcontraceptive(HC)usemayincreasecardiometabolicrisk;however,theeffectofHConemerging
cardiometabolicandotherdiseaseriskfactorsisnotclear.
Objectives: To determine the association between HC use and plasma proteins involved in established and emerging
diseaseriskpathways.
Method: Concentrations of 54 high-abundance plasma proteins were measured simultaneously by LC-MRM/MS in 783
womenfromtheTorontoNutrigenomicsandHealthStudy.C-reactiveprotein(CRP)wasmeasuredseparately.ANCOVAwas
usedtotestdifferencesinproteinconcentrationsbetweenusersandnon-users,andamongHCusersdependingontotal
hormonedose.Linearregressionwasusedtotesttheassociationbetweenduration(years)ofHCuseandplasmaprotein
concentrations.Principalcomponentsanalysis(PCA)wasusedtoidentifyplasmaproteomicprofilesinusersandnon-users.
Results:AfterBonferronicorrection,19proteinsinvolvedininflammation,innateimmunity,coagulationandbloodpressure
regulationweresignificantlydifferentbetweenusersandnon-users(P,0.0009).Thesedifferenceswerereplicatedacross
three distinct ethnocultural groups. Traditional markers of glucose and lipid metabolism were also significantly higher
among HC users. Neither hormone dose nor duration of use affected protein concentrations. PCA identified 4 distinct
proteomicprofilesinusersand3innon-users.
Conclusion: HC use was associated with different concentrations of plasma proteins along various disease-related
pathways,andthesedifferenceswerepresentacrossdifferentethnicities.AsidefromtheknowneffectofHContraditional
biomarkers of cardiometabolic risk, HC use also affects numerous proteins that may be biomarkers of dysregulation i
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