Common TLR1 Genetic Variation Is Not Associated with Death from Melioidosis, a Common Cause of Sepsis in Rural Thailand.docVIP

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Common TLR1 Genetic Variation Is Not Associated with Death from Melioidosis, a Common Cause of Sepsis in Rural Thailand.doc

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Common TLR1 Genetic Variation Is Not Associated with Death from Melioidosis, a Common Cause of Sepsis in Rural Thailand

CommonTLR1GeneticVariationIsNotAssociatedwith DeathfromMelioidosis,aCommonCauseofSepsisin RuralThailand NarisaraChantratita1,2*,SarunpornTandhavanant1,2,NicolleD.Myers3,WirongrongChierakul2,4, VanapornWuthiekanun2,WeeraMahavanakul5,DirekLimmathurotsakul2,6,SharonJ.Peacock1,2,7 T.EoinWest3,8 , 1DepartmentofMicrobiologyandImmunology,FacultyofTropicalMedicine,MahidolUniversity,Bangkok,Thailand,2Mahidol-OxfordTropicalMedicineResearchUnit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, Washington, United States of America, 4Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,5DepartmentofMedicine,SappasithiprasongHospital,UbonRatchathani,Thailand,6DepartmentofTropicalHygiene,FacultyofTropicalMedicine,Mahidol University,Bangkok,Thailand,7DepartmentofMedicine,UniversityofCambridge,Addenbrooke’sHospital,Cambridge,UnitedKingdom,8InternationalRespiratoryand SevereIllnessCenter,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica Abstract Melioidosis,infectioncausedbytheGram-negativebacteriumBurkholderiapseudomallei,isacommoncauseofsepsisin northeastThailand.InwhiteNorthAmericans,commonfunctionalgeneticvariationinTLR1isassociatedwithorganfailure anddeathfromsepsis.WehypothesizedthatTLR1variantswouldbeassociatedwithoutcomesinThaiswithmelioidosis. WecollatedtheglobalfrequenciesofthreeTLR1variantsthatarecommoninwhiteNorthAmericanpopulations:rs5743551 (-7202A/G), rs4833095 (742A/G), and rs5743618 (1804G/T). We noted a reversal of the minor allele from white North AmericansubjectstoAsianpopulationsthatwasparticularlypronouncedforrs5743618.IntheUtahresidentsofEuropean ancestry,thefrequencyofthers5743618Tallelewas17%whereasinVietnamesesubjectsthefrequencywas.99%.We conductedageneticassociationstudyin427patientswithmelioidosistodeterminetheassociationofTLR1variationwith organ failure o