GATA2 Is Associated with Familial Early-Onset Coronary Artery Disease 英文参考文献.docVIP

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GATA2 Is Associated with Familial Early-Onset Coronary Artery Disease 英文参考文献.doc

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GATA2 Is Associated with Familial Early-Onset Coronary Artery Disease 英文参考文献

GATA2IsAssociatedwithFamilialEarly-Onset CoronaryArteryDisease Jessica J.Connelly1,Tianyuan Wang1,Julie E.Cox1,Carol Haynes1,Liyong Wang1,Svati H.Shah1,2,David R.Crosslin1, A.Brent Hale1,SarahNelson1,DavidC.Crossman3,Christopher B.Granger1,JonathanL.Haines4,Christopher J.H.Jones5, JefferyM.Vance1,PascalJ.Goldschmidt-Clermont6,WilliamE.Kraus2,ElizabethR.Hauser1,SimonG.Gregory1* 1DepartmentofMedicineandCenterforHumanGenetics,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStates,2DepartmentofMedicineandDivision ofCardiology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStates,3CardiovascularResearchGroup,NorthernGeneralHospital,UniversityofSheffield, Sheffield, United Kingdom, 4Centerfor Human GeneticsResearch and Department of Molecular Physiology and Biophysics, Vanderbilt University,Nashville, Tennessee, UnitedStates,5UniversityofWalesCollegeofMedicine,Cardiff,UnitedKingdom,6MillerSchoolofMedicine,UniversityofMiami,Miami,Florida,UnitedStates ThetranscriptionfactorGATA2playsanessentialroleintheestablishmentandmaintenanceofadulthematopoiesis.It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelialcellsandsmoothmusclecells.WehaveshownthatGATA2expressionispredictiveoflocationwithinthe thoracicaorta;locationissuggestedtobeasurrogatefordiseasesusceptibility.TheGATA2genemapsbeneaththe Chromosome 3q linkage peak from our family-based sample set (GENECARD) study of early-onset coronary artery disease.Giventheseobservations,weinvestigatedtherelationshipofseveralknownandnovelpolymorphismswithin GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significantassociationoftwoofthesesinglenucleotidepolymorphismsinanindependentcase-controlsamplesetthat wasphenotypicallysimilartotheGENECARDfamilies.Theseobservationsidenti