Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population 英文参考文献.docVIP

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Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population 英文参考文献.doc

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Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population 英文参考文献

SelectionforGeneticVariationInducingPro- InflammatoryResponsesunderAdverseEnvironmental ConditionsinaGhanaianPopulation MarisKuningas1,LindaMay1,RiinTamm2,DavidvanBodegom1,AnitaH.J.vandenBiggelaar3, JohannesJ.Meij4,MarijkeFro¨lich5,JuventusB.Ziem6,HelenaE.D.Suchiman7,AndresMetspalu2,8 ,P. ElineSlagboom7,9,RudiG.J.Westendorp1,9 * 1DepartmentofGerontologyandGeriatrics,LeidenUniversityMedicalCenter,Leiden,TheNetherlands,2DepartmentofBiotechnology,InstituteofMolecularandCell Biology,UniversityofTartu,Tartu,Estonia,3TelethonInstituteforChildHealthResearch,CenterforChildHealthResearch,UniversityofWesternAustralia,Perth,Australia, 4Leyden Academy on Vitality and Ageing, Leiden, The Netherlands, 5Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands, 6SchoolofMedicineandHealthSciences,UniversityofDevelopmentStudies,Tamale,Ghana,7DepartmentofMolecularEpidemiology,LeidenUniversityMedicalCenter, Leiden,TheNetherlands,8EstonianGenomeProjectofUniversityofTartu,Tartu,Estonia,9NetherlandsConsortiumforHealthyAgeing,Leiden,TheNetherlands Abstract Background:Chronicinflammationisinvolvedinthepathogenesisofchronicage-associated,degenerativediseases.Pro- inflammatoryhostresponsesthataredeleteriouslaterinlifemayoriginatefromevolutionaryselectionforgeneticvariation mediatingresistancetoinfectiousdiseasesunderadverseenvironmentalconditions. Methodology/Principal Findings:IntheUpper-EastregionofGhanawhereinfectionhasremainedtheleadingcauseof death,westudiedtheeffectonsurvivalofgeneticvariationsattheIL10genelocusthathavebeenassociatedwithchronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p=0.028) and high TNF-a levels (p=1.3961023), was enriched among Ghanaian elders (p=2.4661026).Furthermore,inanenvironmentwherethesourceofdrinkingwater(wells/riversvs.boreholes)influences mortalityrisks(HR1.28,95%CI[1.09–1.50]),weobservedthatcarriersofthepro-inflammatoryhapl