Genetic Variation in VEGF Does Not Contribute Significantly to the Risk of Congenital Cardiovascular Malformation 英文参考文献.docVIP

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Genetic Variation in VEGF Does Not Contribute Significantly to the Risk of Congenital Cardiovascular Malformation 英文参考文献.doc

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Genetic Variation in VEGF Does Not Contribute Significantly to the Risk of Congenital Cardiovascular Malformation 英文参考文献

GeneticVariationinVEGFDoesNotContribute SignificantlytotheRiskofCongenitalCardiovascular Malformation HelenR.Griffin1,DarrochH.Hall1,AnaTopf1,JamesEden1,A.GrahamStuart2,JonathanParsons3 ,Ian Peart4,JohnE.Deanfield5,JohnO’Sullivan6,SonyaV.Babu-Narayan7,MichaelA.Gatzoulis7,FrancesA. Bu’Lock8,ShoumoBhattacharya9,JamieBentham9,MartinFarrall9,JavierGranadosRiveron10,J.David Brook10,JohnBurn1,HeatherJ.Cordell1,JudithA.Goodship1,BernardKeavney1* 1InstituteofHumanGenetics,NewcastleUniversity,NewcastleuponTyne,UnitedKingdom,2CongenitalHeartCentre,BristolRoyalHospitalforChildren,Bristol,United Kingdom, 3Paediatric Cardiology Unit, Leeds General Infirmary, Leeds, United Kingdom, 4Department of Paediatric Cardiology, Alder Hey Royal Children’s Hospital, Liverpool, United Kingdom, 5Cardiothoracic Unit, Great Ormond Street Hospital, London, United Kingdom, 6Congenital Heart Unit, Cardiothoracic Centre, Freeman Hospital,NewcastleuponTyne,UnitedKingdom,7RoyalBromptonHospitalandNationalHeartLungInstitute,ImperialCollege,London,UnitedKingdom,8Congenital andPaediatricCardiologyService,GlenfieldHospital,Leicester,UnitedKingdom,9DepartmentofCardiovascularMedicine,UniversityofOxford,WellcomeTrustCentre forHumanGenetics,Oxford,UnitedKingdom,10InstituteofGenetics,UniversityofNottingham,Queen’sMedicalCentre,Nottingham,UnitedKingdom Abstract Severalpreviousstudieshaveinvestigatedtheroleofcommonpromotervariantsinthevascularendothelialgrowthfactor (VEGF) gene in causing congenital cardiovascular malformation (CVM). However, results have been discrepant between studiesandnostudytodatehascomprehensivelycharacterisedvariationthroughoutthegene.Wegenotyped771CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF), and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. Wecarried out ameta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare v