Genetic Polymorphisms and the Risk of Accelerated Renal Function Decline in Women 英文参考文献.docVIP

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Genetic Polymorphisms and the Risk of Accelerated Renal Function Decline in Women 英文参考文献.doc

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Genetic Polymorphisms and the Risk of Accelerated Renal Function Decline in Women 英文参考文献

GeneticPolymorphismsandtheRiskofAccelerated RenalFunctionDeclineinWomen CynthiaCooperWorobey1,NaomiD.L.Fisher2,DavidCox3,JohnP.Forman3,4,GaryC.Curhan3,4,5 * 1RenalUnit,DepartmentofMedicine,MassachusettsGeneralHospital,Boston,Massachusetts,UnitedStatesofAmerica,2Endocrine-HypertensionDivision,Department ofMedicine,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,3ChanningLaboratory,DepartmentofMedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 4Renal Division, Department of Medicine, Brigham and Women’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,5DepartmentofEpidemiology,HarvardSchoolofPublicHealth,Boston, Massachusetts,UnitedStatesofAmerica Abstract Background: Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal functiondecline. Methodology/Principal Findings: We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerularfiltrationrate(eGFR)overan11-yearperiodin2578CaucasianparticipantsoftheNurses’HealthStudy.Logistic regressionwasusedtoexaminetheassociationsbetweengenotypeandriskofeGFRdeclineof$25%. Results:After11yearsbetweencreatininemeasurements,theeGFRdeclinedby$25%in423of2578(16%)women.The angiotensinogen (AGT) A-20C polymorphism was associated with a higher risk of renal function decline when two risk alleles were present than if one or no alleles were present (CC vs AA and AC) OR 1.83 (95% CI 1.02–3.26; p=0.04). The angiotensinIItype1receptor(AT1R)A1166Cpolymorphismwasmarginallyassociatedwithahigherriskofrenalfunction decline when two risk alleles were present (CC vs AA, OR=1.41; 95% CI 0.98–2.01; p=0.06). The alpha-ad