Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status 英文参考文献.docVIP

AssociationsbetweenNitricOxideSynthaseGenesand ExhaledNO-RelatedPhenotypesaccordingtoAsthma Status EmmanuelleBouzigon1,2,3,FlorentMonier4,5,MekkiBoussaha1,2,3¤,NicoleLeMoual4,5 He′le`neHuyvaert6,7,Re′gisMatran6,7,Se′bastienLetort1,2,3,JeanBousquet4,8,IsabellePin9,10,11 , , MarkLathrop12,FrancineKauffmann4,5,FlorenceDemenais1,2,3,RachelNadif4,5*,onbehalfofthe EGEACooperativeGroup 1Inserm,U946,Paris,France,2Universite′ ParisDiderot,SorbonneParisCite′, InstitutUniversitaired’He′matologie, Paris,France,3FondationJeanDausset-Centred’Etude du Polymorphisme Humain (CEPH), Paris, France, 4Inserm, U1018, CESP Centre for Research in Epidemiology and Population Health, Respiratory and Environmental EpidemiologyTeam,Villejuif,France, 5Universite′ Paris-Sud 11,UMRS1018,Villejuif,France,6Universite′ LilleNord deFrance,Lille,France, 7CHU,Lille, France,8CHU ArnauddeVilleneuve,Montpellier,France,9Inserm,U823,Epide′miologieenvironnementaleapplique′e a` lareproductionetlasante′ respiratoire,InstitutAlbertBonniot, Grenoble, France, 10Universite′ Joseph Fourier, Grenoble, France, 11Pe′diatrie, CHU de Grenoble, Grenoble, France, 12Commissariat a` l’Energie Atomique, Centre NationaldeGe′notypage,Evry,France Abstract Background:Thenitricoxide(NO)pathwayisinvolvedinasthma,andeosinophilsparticipateintheregulationoftheNO poolinpulmonarytissues.Weinvestigatedassociationsbetweensinglenucleotidepolymorphisms(SNPs)ofNOsynthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma)andbloodeosinophilcounts. Methodology:SNPs(N=121)belongingtoNOS1,NOS2andNOS3genesweregenotypedin1277adultsfromtheFrench EpidemiologicalstudyontheGeneticsandEnvironmentofAsthma(EGEA).Associationanalyseswereconductedonfour quantitative phenotypes: the exhaled fraction of NO (FENO), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2–NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity