TGF-β 1 DNA Polymorphisms, Protein Levels, and Blood Pressure

—Transforming growth factor-β1 (TGF-β1 ), a multifunctional cytokine with fibrogenic properties, has been implicated in the pathogenesis of the vascular and target organ complications of hypertension. TGF-β1 may also regulate blood pressure via stimulation of endothelin-1 and/or renin secretion. Herein we explored the hypothesis that circulating levels of TGF-β1 protein (quantified using a TGF-β1 –specific sandwich ELISA) are correlates of blood pressure levels. This hypothesis was tested in 98 stable end-stage renal disease (ESRD) patients. (The use of ESRD patients as the study cohort eliminates renal function–dependent alterations in circulating levels of TGF-β1 protein.) In addition, in view of the previously reported correlation among TGF-β1 DNA polymorphisms and systolic blood pressure, TGF-β1 codon 25 genotype and alleles were identified in 71 hypertensive subjects and 57 normotensives using amplification refractory mutation system polymerase chain reaction. Our studies demonstrate for the first time that TGF-β1 levels (209±13 ng/mL, mean±SEM) are positive correlates (Pearson correlation analysis) of mean arterial pressure (P =0.008), systolic pressure (P =0.02), and diastolic pressure (P =0.01). We also report that a higher percentage of hypertensives (92%) compared with normotensives (86%) are homozygous for the arginine allele at codon 25. Our observations support the idea that genetically determined TGF-β1 protein concentrations may play a role in blood pressure regulation in humans.