Does over-expression of transforming growth factor-beta account for the increased morbidity in African-Americans?: possible clinical study and therapeutic implications

Abstract

African-Americans experience an excessive prevalence of a number of apparently disparate disorders that all appear to be, at least in part, mediated by the over-expression or activation of transforming growth factor-beta (TGF-beta) signaling pathways, and that certain genotypes including the codon 10 polymorphism occur more commonly among African-Americans and appears to predispose to these disorders. These disorders, fibrosing in nature, include hypertension, focal glomerulosclerosis, diabetic nephropathy, end stage renal disease, sarcoidosis, uterine leiomyoma, keloids, myocardial fibrosis, and glaucoma. The specific polymorphism for TGF-beta, codon 10, has been implicated in glomerulosclerosis and diabetic nephropathy as well as cardiac transplant rejection. Although TGF-beta over-expression is not the sole factor in these disorders, it is suggested that by designing future clinical studies that consider genomic differences in TGF-beta expression, a more complete understanding of these clinical disorders will be possible. A more thorough understanding of the genetic basis of disease will like promote improved therapeutic regimens and may help reduce the disparate health outcomes for African-Americans as well as improve treatment of individuals of various and diverse ethnic backgrounds.