Genetic Susceptibility to Acute Rheumatic Fever A Systematic Review and Meta-Analysis of Twin Studies 英文参考文献.docVIP

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Genetic Susceptibility to Acute Rheumatic Fever A Systematic Review and Meta-Analysis of Twin Studies 英文参考文献.doc

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Genetic Susceptibility to Acute Rheumatic Fever A Systematic Review and Meta-Analysis of Twin Studies 英文参考文献

GeneticSusceptibilitytoAcuteRheumaticFever:A SystematicReviewandMeta-AnalysisofTwinStudies MarkE.Engel1,RaphaellaStander1,JonathanVogel1,AdebowaleA.Adeyemo2,BonganiM.Mayosi1* 1DepartmentofMedicine,GrooteSchuurHospitalandUniversityofCapeTown,CapeTown,SouthAfrica,2CenterforResearchinGenomicsandGlobalHealth,National HumanGenomeResearchInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Abstract Background:Acuterheumaticfeverisconsideredtobeaheritablecondition,butthemagnitudeofthegeneticeffectis unknown.Theobjectiveofthisstudywastoconductasystematicreviewandmeta-analysisoftwinstudiesofconcordance ofacuterheumaticfeverinordertoderivequantitativeestimatesofthesizeofthegeneticeffect. Methods: We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumaticheartdiseaseinmonozygoticversusdizygotictwinsthatusedaccepteddiagnosticcriteriaforacuterheumatic feverandzygositywithoutage,genderorlanguagerestrictions.Twinsimilaritywasmeasuredbyprobandwiseconcordance rateandoddsratio(OR),andaggregateprobandwiseconcordanceriskwascalculatedbycombiningrawdatafromeach study.ORsfromseparatestudieswerecombinedbyrandom-effectsmeta-analysistoevaluateassociationbetweenzygosity statusandconcordance.Heritabilitywasestimatedbyfittingavariancecomponentsmodeltothedata. Results:435twinpairsfromsixindependentstudiesmettheinclusioncriteria.Thepooledprobandwiseconcordancerisk foracuterheumaticfeverwas44%inmonozygotictwinsand12%indizygotictwins,andtheassociationbetweenzygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P,0.001), with no significant study heterogeneity(P=0.768).Theestimatedheritabilityacrossallthestudieswas60%. Conclusions: Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genom