Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion 英文参考文献.docVIP

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Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion 英文参考文献.doc

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Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion 英文参考文献

DifferentialSusceptibilitytoHypertension IsDuetoSelectionduringtheOut-of-Africa Expansion J.Hunter Young1*,Yen-Pei C.Chang1,James Dae-Ok Kim1,Jean-Paul Chretien1,Michael J.Klag1,Michael A.Levine2, Christopher B.Ruff1,Nae-Yuh Wang1,Aravinda Chakravarti1 1TheJohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,2DivisionofPediatrics,TheClevelandClinicFoundation,Cleveland,Ohio, UnitedStatesofAmerica Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variationislargelyunknownbutislikelytoinvolvegenesthatinfluencerenalsalthandlingandarterialvesseltone. Herewearguethatsusceptibilitytohypertensionisancestralandthatdifferentialsusceptibilitytohypertensionisdue to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressurewasclimate,whichproducedalatitudinalclineinheatadaptationand,therefore,hypertensionsusceptibility. Consistentwiththishypothesis,weshowthatecologicalvariables,suchaslatitude,temperature,andrainfall,explain worldwidevariationinheatadaptationasdefinedbysevenfunctionalallelesinfivegenesinvolvedinbloodpressure regulation. The latitudinal cline in heat adaptation is consistent worldwide and is largely unmatched by latitudinal clines in non-functional markers. In addition, we show that latitude and one of these alleles, GNB3 (G protein b3 subunit)825T,accountforamajorportionofworldwidevariationinbloodpressure.Theseresults suggestthatthe currentepidemicofhypertensionisduetoexposuresofthemodernperiodinteractingwithancestralsusceptibility. Modernpopulationsdifferinsusceptibilitytothesenewexposures,however,suchthatthosefromhotenvironments aremoresusceptibletohypertensionthanpopulationsfromcoldenvironments.Thisdifferentialsusceptibilityislikely duetoourhistoryofadaptationtoclimate. Citation:YoungJH,ChangYPC,KimJDO,ChretienJP,KlagMJ,etal.(2005)Differentialsusceptibilitytohypertensionisduetoselectionduringtheout