Polymorphism in NEDD4L Is Associated with Increased Salt Sensitivity, Reduced Levels of P-renin and Increased Levels of Nt-proANP 英文参考文献.docVIP

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Polymorphism in NEDD4L Is Associated with Increased Salt Sensitivity, Reduced Levels of P-renin and Increased Levels of Nt-proANP 英文参考文献.doc

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Polymorphism in NEDD4L Is Associated with Increased Salt Sensitivity, Reduced Levels of P-renin and Increased Levels of Nt-proANP 英文参考文献

PolymorphisminNEDD4LIsAssociatedwithIncreased SaltSensitivity,ReducedLevelsofP-reninandIncreased LevelsofNt-proANP JonasDahlberg.*,Lars-OlofNilsson.,FredrikvonWowern,OlleMelander DepartmentofClinicalSciences,Malmo¨ UniversityHospitalandLundUniversity,Malmo¨,Sweden Objective.Neuronalprecursorcellexpresseddevelopmentallydown-regulated4-like(NEDD4L)isaregulatoroftheamiloride- sensitiveepithelialsodiumchannel(ENaC),thusacandidategeneforsaltsensitivity.CarriersofanintactNEDD4LC2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4Lisassociatedwithincreasedsaltsensitivity.Methods.39normotensivesubjectswerestudied.Thedifferencein24- hoursystolicbloodpressureafterfourweekson150mmol/dayNaClintakeandfourweekson50mmol/dayNaClwasdefined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. Results. Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median,IQR)(18.0,7.5–20.0mmHgvs6.0,0.0–10.0mmHg,P=0.007)andlowerplasmareninconcentration(P-renin)(6.0,2.0– 9.5mU/Lvs15.0,9.0–24.0mU/L,P=0.005)ascomparedtonon-carriersofthesegenotypes.Incarriersofthers4149601GG- genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0– 18.0mmHg vs 5.0, 0.0–10.0mmHg, P=0.07) and P-renin (9.0, 6.0–16.0mU/L vs 15.0, 9.0–28.0mU/L, P=0.03). Conclusion. GeneticNEDD4LvariationseemstoaffectsaltsensitivityandP-renininnormotensivesubjects,suggestingthatgenotypingof NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension. Citation: DahlbergJ,NilssonL-O,vonWowernF,MelanderO(2007)PolymorphisminNEDD4LIsAssociatedwithIncreasedSaltSensitivity,Reduced LevelsofP-reninan