Article ID Journal Published Year Pages File Type
2795431 Cytokine 2010 5 Pages PDF
Abstract

TGFβ1 plasma levels and TGFβ1 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 TGFβ1 genotype, considering several polymorphisms, and in vitro TGFβ1 secretion of human lymphocytes. Four polymorphisms in TGFβ1 (c.-800, c.-509, c.29, c.74) affecting TGFβ1 secretion and a deletion (c.69_77del9) in TGFβR1 influencing TGFβ1 signaling were genotyped in 250 healthy individuals. TGFβ1 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, TGFβ1 levels were obtained for 17 individuals. Mean TGFβ1 levels were 1046.2 pg, 566.7 pg, 740.6 pg, 1001.8 pg, 701.2 pg and 2844 pg per 106 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 TGFβ1/TGFβR1 on secreted TGFβ1 levels in vitro could not be clarified. The inter-individual variation in TGFβ1 levels for individuals with the same genotype was too large to obtain statistically significant differences among genotypes.

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