TGF-beta(1) DNA polymorphisms, protein levels, and blood pressure

Transforming growth factor-beta(1) (TGF-beta(1)), a multifunctional cytokin e with fibrogenic properties, has been implicated in the pathogenesis of th e vascular and target organ complications of hypertension. TGF-beta(1) may also regulate blood pressure via stimulation of endothelin-1 and/or renin s ecretion. Herein we explored the hypothesis that circulating levels of TGF- beta(1) protein (quantified using a TGF-beta(1)-specific sandwich ELISA) ar e correlates of blood pressure levels. This hypothesis was tested in 98 sta ble end-stage renal disease (ESRD) patients. (The use of ESRD patients as t he study cohort eliminates renal function-dependent alterations in circulat ing levels of TGF-beta(1) protein.) In addition, in view of the previously reported correlation among TGF-beta(1) DNA polymorphisms and systolic blood pressure, TGF-beta(1) codon 25 genotype and alleles were identified in 71 hypertensive;subjects and 57 normotensives using amplification refractory m utation system polymerase chain reaction. Our studies demonstrate for the f irst time that TGF-beta(1) levels (209+/-13 ng/mL, mean+/-SEM) are positive correlates (Pearson correlation analysis) of mean arterial pressure (P=0.0 08), systolic pressure (P=0.02), and diastolic pressure (P=0.01). We also r eport that a higher percentage of hypertensives (92%) compared with normote nsives (86%) are homozygous for the arginine allele at codon 25. Our observ ations support the idea that genetically determined TGF-beta(1) protein con centrations may play a role in blood pressure regulation in humans.