differential susceptibility to hypertension is due to selection during the out-of-africa expansion高血压是由于选择的敏感度在走出非洲扩张.pdfVIP

Differential Susceptibility to Hypertension Is Due to Selection during the Out-of-Africa Expansion 1* 1 1 1 1 2 J. Hunter Young , Yen-Pei C. Chang , James Dae-Ok Kim , Jean-Paul Chretien , Michael J. Klag , Michael A. Levine , 1 1 1 Christopher B. Ruff , Nae-Yuh Wang , Aravinda Chakravarti 1 The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Division of Pediatrics, The Cleveland Clinic Foundation, Cleveland, Ohio, United States of America Hypertension is a leading cause of stroke, heart disease, and kidney failure. The genetic basis of blood pressure variation is largely unknown but is likely to involve genes that influence renal salt handling and arterial vessel tone. Here we argue that susceptibility to hypertension is ancestral and that differential susceptibility to hypertension is due to differential exposure to selection pressures during the out-of-Africa expansion. The most important selection pressure was climate, which produced a latitudinal cline in heat adaptation and, therefore, hypertension susceptibility. Consistent with this hypothesis, we show that ecological variables, such as latitude, temperature, and rainfall, explain worldwide variation in heat adaptation as defined by seven functional alleles in five genes involved in blood pressure 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, account for a major portion of worldwide variation in blood pressure. These results suggest that the