Transforming growth factor beta and progression of renal disease

End-stage renal disease (ESRD) is more frequent in African Americans compared to whites. Many factors may be responsible, including genetic differences, increased prevalence of risk factors, and socioeconomic factors; however, to date, these proposed genetic or environmental factors have not provided a satisfactory explanation for the increased risk of ESRD in African Americans. Because renal fibrosis is a correlate of progressive renal failure and a dominant feature of ESRD, and because transforming growth factor beta 1 (TGF-beta(1)) can induce fibrosis and renal insufficiency, we explored the hypothesis that TGF-beta(1) hyperexpression is more frequent in African Americans compared to whites. We tested our hypotheses by measuring TGF-beta(1) levels in African Americans and white patients with ESRD, hypertension, and in normal patients. In hypertensive and normal patients, we also evaluated TGF-beta(1) mRNA levels, and TGF-beta(1) DNA polymorphisms. We demonstrated that circulating levels of TGF-beta(1) are higher in African American ESRD patients, hypertensive patients, and normal control patients compared to their white counterparts. We also reported that TGF-beta(1) mRNA levels are higher in hypertensives compared to normotensives. Our preliminary genetic analyses suggest that TGF-beta(1) DNA polymorphisms may distinguish hypertensives from normotensives, and our laboratory is currently investigating racial differences in TGF-beta(1) DNA polymorphisms. Our observations of hyperexpression of TGF-beta(1) in African Americans suggest a mechanism for the increased prevalence of renal failure and hypertensive target organ damage in this population.