Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population 英文参考文献.docVIP

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Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population 英文参考文献.doc

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Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population 英文参考文献

CandidateHumanGeneticPolymorphismsandSevere MalariainaTanzanianPopulation AlphaxardManjurano1,2.,TaaneG.Clark2,3.,BehzadNadjm1,2,GeorgeMtove1,HannahWangai1, NunoSepulveda3,SusanaG.Campino4,CarolineMaxwell2,RaimosOlomi1,KirkR.Rockett5, AnnaJeffreys5,MalariaGenConsortium,EleanorM.Riley2,HughReyburn1,2,ChristopherDrakeley1,2 * 1JointMalariaProgramme,KilimanjaroChristianMedicalCentre,Moshi,Tanzania,2FacultyofInfectiousandTropicalDiseases,LondonSchoolofHygieneandTropical Medicine, London, United Kingdom, 3Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom, 4WellcomeTrustSangerInstitute,Hinxton,Cambridge,UnitedKingdom,5WellcomeTrustCentreforHumanGenetics,UniversityofOxford,Oxford,UnitedKingdom Abstract Humangeneticbackgroundstronglyinfluencessusceptibility tomalariainfectionandprogressiontoseverediseaseand death.Classicalgeneticstudiesidentifiedhaemoglobinopathiesanderythrocyte-associatedpolymorphisms,asprotective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP’s, previously associatedwithalteredriskofmalaria,betweenTanzanianchildrenwithandwithoutseveremalaria.Fivehundredchildren, aged1–10years,withseveremalariawererecruitedfromthoseadmittedtohospitalinMuheza,Tanzaniaandcompared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletionsinthealpha-thalassaemiagene.SNPsintwoX-linkedgeneswereassociatedwithalteredriskofseveremalariain femalesbutnotinmales:heterozygosityforoneorotheroftwoSNPsintheG6PDgenewasassociatedwithprotection fromallformsofseverediseasewhilsttwoSNPsinthegeneencodingCD40Lwereassociatedwithrespiratorydistress.A SNPintheadenylcyclase9(ADCY9)genewasassociatedwithprotectionfromacidosiswhilstapolymorphismintheIL-1a gene(IL1A)wasassociatedwithanincreasedriskofacidosis.SNPsinthe