Promoter Variation in the DC-SIGN–Encoding Gene CD209 Is Associated with Tuberculosis 英文参考文献.docVIP

o PL SMEDICINE PromoterVariationintheDC-SIGN–Encoding GeneCD209IsAssociatedwithTuberculosis Luis B.Barreiro1,2,Olivier Neyrolles2,Chantal L.Babb3,Ludovic Tailleux2,He′le`neQuach1,Ken McElreavey4, Paul D.van Helden3,Eileen G.Hoal3,Brigitte Gicquel2,Llu?′sQuintana-Murci1* 1CNRSFRE2849,UnitofMolecularPreventionandTherapyofHumanDiseases,InstitutPasteur,Paris,France,2Unite′deGe′ne′tiqueMycobacte′rienne,InstitutPasteur,Paris, France,3FacultyofHealthSciences,StellenboschUniversity,Tygerberg,SouthAfrica,4Reproduction,Fertilite′ etPopulations,InstitutPasteur,Paris,France CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. ABSTRACT Background AuthorContributions:LBB,ON,BG, andLQdesignedthestudy.LBB,ON, LT,KM,BG,andLQanalyzedthe data.LBB,CLB,andHQperformed thesequencingandgenotyping analyses.PDHandEGHcoordinated thecollection,clinicalinformation, andDNAextractionofthecohort samples.LBB,ON,CLB,LT,HQ,KM, PDH,EGH,BG,andLQcontributedto writingthepaper. Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosisreceptoronhumandendriticcells.WereasonedthatifDC-SIGNinteractswithM. tuberculosis,aswellaswithotherpathogens,variationinthisgenemighthaveabroadrangeof influenceinthepathogenesisofanumberofinfectiousdiseases,includingtuberculosis. MethodsandFindings We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (à871G and à336A) and decreasedriskofdevelopingtuberculosis.Bylookingatthegeographicaldistributionofthese variants,weobservedthattheiralleliccombinationismainlyconfinedtoEurasianpopulations. Citation:BarreiroLB,NeyrollesO, BabbCL,TailleuxL,QuachH,etal.