COPD基因和基因组学研究进展

COPD1410013〔〕〔〕R563.9R394.3〔〕A〔〕1005-9202201117-3413-043087135130870916NCET-08056309JJ100511973-。1962-。1976-、。chronicobstructivepulmonarydiseaseCOPD、。COPDWHO2030COPD〔1〕。COPD〔2〕。COPD10%～20%COPD〔3〕COPD。HapMapCOPD。COPD。1candidategenesstudyCOPD。、COPD。COPD、、、、〔23〕。COPD1proteaseinhibitor1PIα1-SERPINA1。PI14q32.11%～2%COPDα1-〔4〕。PICOPD6～50〔5〕。HumanUnidentifiedGene-EncodedHUGE9489COPD42735COPD。13COPD。〔6〕。Hersh12COPD29BThr131Ile、GT、tumornecrosisfactorTNF-308G＞A、“”His139ArgCOPD〔7〕。Smolonska20COPD5〔3β1TGFβ1、GSTM11IL1RN〕COPD〔8〕。Castaldi72COPDmetaTGFβ1rs1800470、GSTM1Nullallele、SOD3rs1799896TNFrs1800629COPD〔9〕。、COPD/、、、、、、。〔23〕。2Genome-widelinkageanalysis。。COPD。COPD。、、COPDCOPD〔23〕。1/FEV1/FVC42。6q、21p4p18。COPD72585。12q、1922COPD。2qFEV1/FVC。FEV1/FVCFEF25%～75%2q12pCOPD。2q5qFEV1/FVC。Celedon19q〔10〕。·3143·COPD174SERPINE2COPDSNP2q〔1112〕。SERPINE2COPD。Chappell〔13〕。。COPD。。。HershCOPD2qDNAX-rayrepaircomplementingde-fectiveinChinesehamster5XRCC5COPD〔2314〕。COPD6q〔2315〕6qthese-cretedmodularcalcium-bindingprotein2SMOC2COPD。WilkSMOCSNPSMOC6q〔16〕。19q13TGFβ1SNPCOPDTGFβ1〔10〕。1COPD3〔34〕OMIM1α1-14q32.1PISERPINA111074001-A314q32.1SERPINA3110728072q33-q35PI7SERPINE2177010920q11.2-q13.1MMP9120361-3320p13ADAM33607114-S-M11p13.3GSTM11138350-S-P111q13GSTP11134660-S-T122q11.2GSTT16004361q42.1EPHX1113281022q12HMOX1114125034p15.3-p15.1SOD3185490D4q12GC1139200-β19q13.1TGFβ111901806p21.3TNF1191160101q31-q32IL101124092α-6p21.3LTA153440-B2p11-12.1SFTPB11786406p21.3HLA1428007q31.2CFTR1602421β25q32-q34ADRB210969015COPD。COPD。16p10p、6q21q、2q、20q12q5p〔2〕COPD。3genome-wideassociationstudiesGWASHapMapGWAS。GWASSNPSNP。GWAS、、〔1718〕。GWAS2COPD4COPD。Pillai823COPD81015SNPrs8034191COPD。4HhhedgehoginteractingproteinHHIPFEV1/FVCCOPD〔1920〕。rs8034191CHRNA3CHRNA5iron-bindingproteinIREB2〔19〕。COPD〔20〕。32940COPD1380GWAS4q22.1familywithsequencesimilarity13memberAFAM13ACOPD〔21〕GWAS〔22〕。FAM13A。PillaiCHRNA3-CHRNA5-IREB2HHIP〔1921〕。GWAS。1070987SNP。SNP。COPDCFTR、SOD3GC。SNP〔23〕。7691FEV1/FVC〔24〕。4q4SNPFEV1/FVCSNPFEV1/FVC。SNPCOPD〔19〕。SNP4q31HHIP。CHINA3/5。Hancock420890GWAS8FEV1/FVCHHIP、GPR126、ADAM19、AGER-PPT2、FAM13A、PTCH1、PID1HTR41FEV1INTS12-GSTCD-NPNT〔22〕。GWAS54q24GSTCD、2q35TNS15q33HTR4FEV16p21AGERDAMM215q23THSD4FEV1/FVC〔25〕。CHRNA3-CHRNA5-CHRNB4、、COPD〔1925〕。·4143·2011931COPDGWAS415〔19〕。GWAS〔18〕COPDCOPDGWASCOPD。4gene-expressionstudies/COPD。COPD、。4COPD〔26〕。SteilingCOPDMicroRNACOPD〔27〕。BhattacharyaCOPD220COPD〔28〕COPDCOPD〔29〕。“”COPD。COPD〔20〕。PierrouCOPD200〔30〕COPD〔2930〕。DeMeoCOPD889SNP15q25.1IREB2ironregulatorypro-tein2COPDCOPDmR-NA〔31〕。TilleyNotchCOPD〔32〕。HapMapCOPD。COPD、COPDCOPD。COPDCOPD。51WorldHealthOrganizationWHO.Globalburdenofdisease2004up-date〔Internet〕.GenevaWHO2008accessed2010June10pp.23.Availablefromhttp//éY.Geneticsofchronicobstructivepulmonarydiseaseasuccinctre-viewfutureavenuesandprospectiveclinicalapplications〔J〕.Pharma-cogenomics2009104655-67.3SeifartCPlagensA.Geneticsofchronicobstructivepulmonarydisease〔J〕.IntJChronObstructPulmonDis200724541-50.4GanrotPOLaurellCBErikssonS.Obstructivelungdiseaseandtrypsininhibitorsinalpha-1-antitrypsindeficiency〔J〕.ScandJClinLabInvest1967193205-8.5ChappellSDalyLMorganKetal.CryptichaplotypesofSERPINA1confersusceptibilitytochronicobstructivepulmonarydisease〔J〕.HumMutat2006271103-9.6LohmuellerKEPearceCLPikeMetal.Meta-analysisofgeneticassoci-ationstudiessupportsacontributionofcommonvariantstosusceptibilitytocommondisease〔J〕.NatGenet2003332177-82.7HershCPDemeoDLLangeCetal.Attemptedreplicationofreportedchronicobstructivepulmonarydiseasecandidategeneassociations〔J〕.AmJRespirCellMolBiol200533171-8.8SmolonskaJWijmengaCPostmaDSetal.Meta-analysesonsuspectedchronicobstructivepulmonarydiseasegenesasummaryof20years're-search〔J〕.AmJRespirCritCareMed20091807618-31.9CastaldiPJChoMHCohnMetal.TheCOPDgeneticassociationcom-pendiumacomprehensiveonlinedatabaseofCOPDgeneticassociations〔J〕.HumMolGenet2010193526-34.10CeledonJCLangeCRabyBAetal.Thetransforminggrowthfactor-βTGFβ1geneisassociatedwithchronicobstructivepulmonarydiseaseCOPD〔J〕.HumMolGenet200413151649-56.11DeMeoDLMarianiTJLangeCetal.TheSERPINE2geneisassociat-edwithchronicobstructivepulmonarydisease〔J〕.AmJHumGenet2006782253-64.12ZhuGWarrenLAponteJetal.TheSERPINE2geneisassociatedwithchronicobstructivepulmonarydiseaseintwolargepopulations〔J〕.AmJRepirCritCareMed20071762167-73.13ChappellSDalyLMorganKetal.TheSERPINE2geneandchronicobstructivepulmonarydisease〔J〕.AmJHumGenet2006791184-6.14HershCPPillaiSGZhuGetal.Multistudyfinemappingofchromo-some2qidentifiesXRCC5asaCOPDSusceptibilityGene〔J〕.AmJRespirCritCareMed20101825605-13.15WilkJBDeStefanoALJoostOetal.Linkageandassociationwithpul-monaryfunctionmeasuresonchromosome6q27intheFraminghamHeartStudy〔J〕.HumMolGenet200312212745-51.16WilkJBHerbertAShoemakerCMetal.Secretedmodularcalcium-bindingprotein2haplotrpesareassociatedwithpulmonaryfunction〔J〕.AmJRespirCritCareMed20071756554-60.17ManolioTABrooksLDCollinsFS.AHapMapharvestofinsightsintothegeneticsofcommondisease〔J〕.JClinInvest200811851590-605.18Hi