Genetic control of the circulating concentration of transforming growth factor type beta1

Abstract

The concentration of transforming growth factor beta (TGF-beta) in plasma has been correlated with the development of several diseases, including atherosclerosis and certain forms of cancer. However, the mechanisms that control the concentration of TGF-beta in plasma are poorly understood. In a study of 170 pairs of female twins (average age 57.7 years) we show that the concentration of active plus acid-activatable latent TGF-beta1 [(a+l) TGF-beta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-beta1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G-->A at position -800 bp and C-->T at position -509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF-beta1, explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1 concentration. It is therefore possible that predisposition to atherosclerosis, bone diseases or various forms of cancer may be correlated with the presence of particular alleles at the TGFB1 locus.

Association Between EGF, TGF-β1 and TNF-α Gene Polymorphisms and Hepatocellular Carcinoma

“…Grainger reported that individuals homozygous for -509T/T had higher plasma concentrations of TGF-β1 than heterozygous C/T or homozygous C/C individuals (Grainger et al, 1999). The genotype distribution and allele frequencies among the healthy controls in our study were parallel to the literature.…”

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

“…Twin studies are a useful tool to assess the heritability of cytokine production. 21 Our results confirm a considerable genetic component for IL-10 production upon LPS stimulation with a heritability of 0.5. This means that 50% of IL-10 production are determined by genetic factors whereas the other half is accounted for by additive environmental influences.…”

No association between SNPs regulating TGF-β1 secretion and late radiotherapy toxicity to the breast: Results from the RAPPER study

“…The two SNPs have been reported to act by altering the rate of secretion of TGFB1 and hence the circulating levels of mature protein [33][34][35][36]. However, not all studies have demonstrated such a relationship [37] -the presence, in the circulation, of both latent and activated forms may complicate the interpretation of studies on circulating levels.…”