Abstract 165: Angiotensinogen M235T Modifies the Relationship between PAI-1 and Renal Blood Flow in Caucasian Hypertensive Individuals

Abstract

Studies have reported an association of angiotensinogen (AGT) gene polymorphisms with hypertension and renal blood flow (RBF). The T allele of rs699 (AGT 235T) is associated with increased levels of angiotensinogen and reduced RBF. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic pathway. Elevated PAI-1 is associated with increased renin-angiotensin system (RAS) activity and cardiovascular damage. We hypothesized that hypertensive individuals with the TT genotype of AGT 235 would display higher levels of PAI-1. We further hypothesized an inverse relationship would be observed between PAI-1 and RBF, and that the strength of this correlation would be dependent on genotype status. A total of 159 Caucasian hypertensive participants (mean age 49.3y, BMI 27.6) had data available for AGT235, PAI-1 and RBF from the HyperPATH study. RBF was measured by para-aminohippurate clearance method while on a liberal salt diet (>200 mmol Na/day for 1 week). Genotype frequencies were in Hardy-Weinberg Equilibrium (MM 41/MT 94/TT 24). Multivariate regression demonstrated the TT genotype was associated with higher PAI-1 levels compared with MT + MM (41.0±8.1 v. 26.9±7.1ng/ml, p=0.005). Genotype status modified the relationship between PAI-1 and RBF whereby only the TT genotype showed a significant correlation after adjusting for age, BMI and BP (TT pr2=0.22, Beta= -1.66 p=0.001 v. MT+MM pr2=0.05, Beta= -0.82, p=0.21). AGT 235T is associated with elevated PAI-1 and influences the relationship between PAI-1 and RBF in Caucasian hypertensives. This provides mechanistic clues to explain the genetic underpinnings involving AGT polymorphisms and hypertension.