Genetic analysis of blood pressure and blood pressure response to orthostatic stress: are the same genes involded in both traits?
Aim: Our aim was to investigate genetic involvement in systolic and diastolic blood pressure (SBP and DBP) responses to orthostatic stress.Methods: Data from 453 members of 4 large kindreds, each ascertained through a white male with essential hypertension, were used. Blood pressures were measured seated, supine (SBP mean = 111mmHg and DBP mean = 68 mmHg), and at 1-, 2- and 3- minutes of 70-degree head-up tilt. A variance components analytical approach implemented in the SOLAR statistical genetic analytical package was used. Sex, age and age squared were covariates in all of the models. Bivariate analyses were conducted to examine pleiotropy between supine blood pressures with those at 1-, 2-, and 3-minutes of tilt. Likelihood ratio tests were used to evaluate different genetic models. Results: For SBP the covariates explained 10 to 15 percent of the phenotypic variance. Significant heritabilities were observed for seated and supine blood pressures; e.g., 0.29 and 0.31 respectively for SBP. Blood pressures resulting from the baroreceptor reflex response to arterial pressure change induced by tilt had comparable heritabilities; e.g., at 1-, 2- and 3-minutes post-tilt they were 0.24, 0.29, and 0.36, respectively for SPB. Similarly, the blood pressure response, the change in blood pressure from supine to tilt, had modest heritabilities of 0.08 (n.s.), 0.16, and 0.19 respectively for SBP, and 0.13, 0.08 (n.s.), and 0.16 for DBP. For both SBP and DBP, the bivariate models testing for pleotropy between the supine pressure and the pressure at each minute of tilt showed that there was no evidence for differential gene expression for blood pressure in these two conditions. Conclusions: Resting levels of blood pressure, the levels reached in response to orthostatic stress, and the actual change in blood pressure resulting from that stress are heritable. The genes that are involved in establishing the control of resting supine blood pressure do not differ from those that are involved in mediating the first 3 minutes of blood pressure response to an orthostatic stress of 70-degree head-up tilt (i.e., there is complete pleiotropy for these traits).