Blood pressure response to angiotensin II, low-density lipoprotein cholesterol and polymorphisms of the angiotensin II type 1 receptor gene in hypertensive sibling pairs
Genome-Wide Association Study
Blood pressure (BP) response to infused angiotensin II (Ang II) has been widely used to characterize hypertensive subjects. High cholesterol levels have recently been found to enhance this response in young men, suggesting an important new link between atherosclerosis and hypertension. The present study assessed the familial resemblance of the BP response following an Ang II infusion and measured the factors affecting the trait in a large set of hypertensive men and women. After a low-salt diet for 7 days a 30-min infusion of Ang II was administered to 218 white hypertensive patients (28 singletons, 80 sibling pairs, 10 trios). Age and gender were significantly correlated to the Ang II systolic but not to the diastolic BP response. Conversely, cholesterol level and especially low-density lipoprotein (LDL) were correlated to both systolic and diastolic changes. Multivariate analysis showed that age, gender, and LDL were the three parameters that explained the systolic BP change whereas plasma LDL remained the only variable significantly correlated to the diastolic BP change. Significant familial resemblances in the Ang II induced systolic and diastolic BP response were observed, especially in female pairs. On this limited number of subjects, suggestive evidence for association and linkage was found between the trait, A1166C, and (CA)n repeat polymorphisms of the Ang II type 1 receptor (AT1R) gene. In conclusion, the Ang II induced BP change is strongly related to plasma LDL in hypertensive men and women, stressing the importance of the lipid profile as a contributor to BP regulation. Familial resemblance of this intermediate phenotype is sex dependent and may be partly explained by polymorphisms of the AT1R gene.