Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity 英文参考文献.docVIP

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Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity 英文参考文献.doc

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Histo-Blood Group Gene Polymorphisms as Potential Genetic Modifiers of Infection and Cystic Fibrosis Lung Disease Severity 英文参考文献

Histo-BloodGroupGenePolymorphismsasPotential GeneticModifiersofInfectionandCysticFibrosisLung DiseaseSeverity JenniferL.Taylor-Cousar1*,MaimoonaA.Zariwala2,LauranellH.Burch3,RhondaG.Pace2,MitchellL. Drumm6,HollinCalloway2,HaiyingFan5,BrentW.Weston5,FredA.Wright4,MichaelR.Knowles2forthe GeneModifierStudyGroup 1University of New Mexico Health Sciences Center, Pulmonary Divisions, Internal Medicine and Pediatrics, Albuquerque, New Mexico, United States of America, 2University ofNorth Carolina,Cystic Fibrosis/PulmonaryResearchandTreatment Center,ChapelHill,NorthCarolina, UnitedStates ofAmerica, 3NationalInstitute of EnvironmentalHealthSciences,ResearchTrianglePark,NorthCarolina,UnitedStatesofAmerica,4UniversityofNorthCarolina,DepartmentofBiostatistics,ChapelHill, NorthCarolina,UnitedStatesofAmerica,5UniversityofNorthCarolina,Hematology-Oncology,DepartmentofPediatrics,ChapelHill,NorthCarolina,UnitedStatesof America,6CaseWesternReserveUniversity,PediatricPulmonaryDivision,DepartmentofPediatrics,Cleveland,Ohio,UnitedStatesofAmerica Abstract Background: The pulmonary phenotype in cystic fibrosis (CF) is variable; thus, environmental and genetic factors likely contribute toclinical heterogeneity.Wehypothesized thatgeneticallydeterminedABOhisto-bloodgroupantigen(ABH) differencesinglycosylationmayleadtodifferencesinmicrobialbindingbyairwaymucus,andthuspredisposetoearlylung infectionandmoreseverelungdiseaseinasubsetofpatientswithCF. Methods and Principal Findings: Clinical information and DNA was collected on .800 patients with the DF508/DF508 genotype.Patientsinthemostsevereandmildestquartilesforlungphenotypewereenrolled.Bloodsamplesunderwent lymphocyte transformation and DNA extraction using standard methods. PCR and sequencing were performed using standard techniques to identify the 9 SNPs required to determine ABO blood type, and to identify the four SNPs that account for 90–95% of Lewis status in Caucasians. Allele identification of the one nonsynonymous SNP in FUT2