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(Hypertension. 2009;53:262.)
© 2009 American Heart Association, Inc.

Original Articles

Stress-Induced Sodium Excretion

A New Intermediate Phenotype to Study the Early Genetic Etiology of Hypertension?

Dongliang Ge; Shaoyong Su; Haidong Zhu; Yanbin Dong; Xiaoling Wang; Gregory A. Harshfield; Frank A. Treiber; Harold Snieder

From the Georgia Prevention Institute (D.G., H.Z., Y.D., X.W., G.A.H., F.A.T., H.S.), Department of Pediatrics, Medical College of Georgia, Augusta; Division of Cardiology (S.S.), Department of Medicine, Emory University School of Medicine, Atlanta, Ga; Twin Research and Genetic Epidemiology Unit (H.S.), King’s College, London, United Kingdom; and the Unit of Genetic Epidemiology and Bioinformatics (H.S.), Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Correspondence to Harold Snieder, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail h.snieder{at}epi.umcg.nl

Impaired stress-induced pressure natriuresis, ie, an inadequate compensatory increase in urinary sodium excretion (U_NaV) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline U_NaV, stress U_NaV, and the U_NaV response to stress (U_NaV=stress U_NaV– baseline U_NaV), we studied 396 black and 494 white twins, including monozygotic and dizygotic twins of the same as well as the opposite sex (mean age: 17.6±3.3 years; range: 11.9 to 30.0 years). Bivariate genetic model fitting was performed to examine the extent to which genetic and environmental factors are common or specific to baseline and stress U_NaV. Heritability estimates for U_NaV can be derived from these bivariate models. All of the bivariate analyses were performed separately in whites and blacks, because univariate models for baseline U_NaV showed significant ethnic differences in heritability estimates. Best-fitting models showed that the heritability of stress U_NaV was 0.42 in whites and 0.58 in blacks. Only 15% and 11% of the total variance could be attributed to genetic factors common to baseline and stress U_NaV in whites and blacks, respectively. After removal of all of the shared influences with baseline U_NaV, heritabilities for stress U_NaV were 0.32 in whites and 0.57 in blacks. Heritability estimates for U_NaV were 0.36 in whites and 0.39 in blacks. In summary, this study establishes U_NaV and stress U_NaV as heritable phenotypes that may be used to study the genetic etiology of early hypertension development.

Key Words: natriuresis • blood pressure • risk factors • genetics • twin study • black