BackgroundMostpersonswhoarehomozygousforC282Y,theHFEallelemostcommonlyasssociatedwithhereditaryhemochromatosis,haveelevatedlevelsofserumferritinandtransferrinsaturation.DiseasesrelatedtoironoverloaddevelopinsomeC282Yhomozygotes,buttheextentoftheriskiscontroversial.
MethodsWeassessedHFEmutationsin31,192personsofnorthernEuropeandescentbetweentheagesof40and69yearswhoparticipatedintheMelbourneCollaborativeCohortStudyandwerefollowedforanaverageof12years.Inarandomsampleof1438subjectsstratifiedaccordingtoHFEgenotype,includingall203C282Yhomozygotes（ofwhom108werewomenand95weremen）,weobtainedclinicalandbiochemicaldata,includingtwosetsofironmeasurementsperformed12yearsapart.Diseaserelatedtoironoverloadwasdefinedasdocumentedironoverloadandoneormoreofthefollowingconditions:cirrhosis,liverfibrosis,hepatocellularcarcinoma,elevatedaminotransferaselevels,physician-diagnosedsymptomatichemochromatosis,andarthropathyofthesecondandthirdmetacarpophalangealjoints.ResultsTheproportionofC282Yhomozygoteswithdocumentediron-overloadCrelateddiseasewas28.4%（95%confidenceinterval[CI],18.8to40.2）formenand1.2%（95%CI,0.03to6.5）forwomen.Onlyonenon-C282Yhomozygote（acompoundheterozygote）haddocumentediron-overloadCrelateddisease.MaleC282Yhomozygoteswithaserumferritinlevelof1000µgperliterormoreweremorelikelytoreportfatigue,useofarthritismedicine,andahistoryofliverdiseasethanweremenwhohadthewild-typegene.ConclusionsInpersonswhoarehomozygousfortheC282Ymutation,iron-overloadCrelateddiseasedevelopedinasubstantialproportionofmenbutinasmallproportionofwomen.全文链接：http://content.nejm.org/cgi/content/full/358/3/221
