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-beta1) can induce fibrosis and renal insufficiency, we explored the hypothesis that TGF-beta1 hyperexpression is more frequent in African Americans compared to whites. We tested our hypotheses by measuring TGF-beta1 levels in African Americans and white patients with ESRD, hypertension, and in normal patients. In hypertensive and normal patients, we also evaluated TGF-beta1 mRNA levels, and TGF-beta1 DNA polymorphisms. We demonstrated that circulating levels of TGF-beta1 are higher in African American ESRD patients, hypertensive patients, and normal control patients compared to their white counterparts. We also reported that TGF-beta1 mRNA levels are higher in hypertensives compared to normotensives. Our preliminary genetic analyses suggest that TGF-beta1 DNA polymorphisms may distinguish hypertensives from normotensives, and our laboratory is currently investigating racial differences in TGF-beta1 DNA polymorphisms. Our observations of hyperexpression of TGF-beta1 in African Americans suggest a mechanism for the increased prevalence of renal failure and hypertensive target organ damage in this population.
August
Phyllis
P
Weill Medical College of Cornell University, New York, New York 10021, USA. paugust@med.cornell.edu
Suthanthiran
Manikkam
M
D001741:Black or African American / Q000706:statistics & numerical data*; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000097:blood / Q000208:ethnology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000208:ethnology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D044465:White People / Q000706:statistics & numerical data*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1