Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression 英文参考文献.docVIP

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Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression 英文参考文献.doc

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Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression 英文参考文献

GeneticVariantsinNuclear-EncodedMitochondrial GenesInfluenceAIDSProgression SherL.Hendrickson1*,JamesA.Lautenberger1,LeslieWeiChinn1,MichaelMalasky2,EfeSezgin1, LawrenceA.Kingsley3,JamesJ.Goedert4,GregoryD.Kirk5,EdwardD.Gomperts6,SusanP. Buchbinder7,JenniferL.Troyer2,StephenJ.O’Brien1 1Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland, United States of America, 2Laboratory of Genomic Diversity, SAIC-Frederick, Inc., Frederick, Maryland, United States of America, 3Department of Infectious Diseases and Microbiology and Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4Infections and Immunoepidemiology Branch, National Cancer Institute, Bethesda, Maryland, United States of America,5TheDepartmentofEpidemiology,JohnsHopkinsBloombergSchoolofPublicHealth,Baltimore,Maryland,UnitedStatesofAmerica,6DivisionofHematology/ Oncology,Children’sHospitalofLosAngeles,LosAngeles,California,UnitedStatesofAmerica,7SanFranciscoCityClinic,DepartmentofPublicHealth,SanFrancisco, California,UnitedStatesofAmerica Abstract Background:Thehumanmitochondrialgenomeincludesonly13codinggeneswhilenuclear-encodedgenesaccountfor 99%ofproteinsresponsibleformitochondrialmorphology,redoxregulation,andenergetics.Mitochondrialpathogenesis occursinHIVpatientsandgenetically,mitochondrialDNAhaplogroupswithpresumedfunctionaldifferenceshavebeen associatedwithdifferentialAIDSprogression. Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1infectedpatients.WeexaminedNEMPsforassociationwiththerateofAIDSprogressionusinggenotypesgenerated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotypedSNPsgave50%orbetterhaplotypecoveragefor679ofknownNEMPgenes.WithaBonferroniadjustmentfor thenumbe