Association of TGFbeta1 polymorphisms involved in radiation toxicity with TGFbeta1 secretion in vitro.
TGFbeta1 plasma levels and TGFbeta1 genetic polymorphisms have been linked to radiation-induced lung injury. As the correlation between plasma levels and genotype is not always straightforward, this study investigated the association between TGFbeta1 genotype, considering several polymorphisms, and in vitro TGFbeta1 secretion of human lymphocytes. Four polymorphisms in TGFbeta1 (c.-800, c.-509, c.29, c.74) affecting TGFbeta1 secretion and a deletion (c.69_77del9) in TGFbetaR1 influencing TGFbeta1 signaling were genotyped in 250 healthy individuals. TGFbeta1 levels were determined for 10 individuals with wild type alleles for all considered polymorphisms and for 21 individuals harboring variant alleles of a single polymorphism and no variant alleles at any other considered polymorphic location. After cell proliferation and cell viability quality control criteria, TGFbeta1 levels were obtained for 17 individuals. Mean TGFbeta1 levels were 1046.2pg, 566.7pg, 740.6pg, 1001.8pg, 701.2pg and 2844pg per 10(6)cells for, respectively, c.-800 heterozygous, c.-509/c.29 heterozygous, c.-509/c.29 homozygous variant, c.69_77del9 heterozygous and c.69_77del9 homozygous variant cells. Only for c.-800 heterozygous cells this difference was borderline statistically significant compared to wild type cells (p=0.071). In conclusion, the effect of genetic polymorphisms in TGFbeta1/TGFbetaR1 on secreted TGFbeta1 levels in vitro could not be clarified. The inter-individual variation in TGFbeta1 levels for individuals with the same genotype was too large to obtain statistically significant differences among genotypes.
Department of Basic Medical Sciences, Ghent University, Belgium. kim.deruyck@UGent.be
De Ruyck
DR
Kim
Beels
B
Laurence
Van Meerbeeck
VM
Jan
De Neve
de N
Wilfried
Thierens
T
Hubert
D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011832:Radiation Injuries / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I