Genetics Stress-Induced Sodium Excretion A New Intermediate Phenotype to Study the Early Genetic Etiology of Hypertension?

Impaired stress-induced pressure natriuresis, ie, an inadequate compensatory increase in urinary sodium excretion (UNaV) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline UNaV, stress UNaV, and the UNaV response to stress ( UNaV stress UNaV baseline UNaV), 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 UNaV. Heritability estimates for UNaV can be derived from these bivariate models. All of the bivariate analyses were performed separately in whites and blacks, because univariate models for baseline UNaV showed significant ethnic differences in heritability estimates. Best-fitting models showed that the heritability of stress UNaV 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 UNaV in whites and blacks, respectively. After removal of all of the shared influences with baseline UNaV, heritabilities for stress UNaV were 0.32 in whites and 0.57 in blacks. Heritability estimates for UNaV were 0.36 in whites and 0.39 in blacks. In summary, this study establishes UNaV and stress UNaV as heritable phenotypes that may be used to study the genetic etiology of early hypertension development. (Hypertension. 2009;53:262-269.)