科研之友
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摘要
TGF beta 1 plasma levels and TGF beta 1 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 TGF beta 1 genotype, considering several polymorphisms, and in vitro TGF beta 1 secretion of human lymphocytes. Four polymorphisms in TGF beta 1 (c.-800, c.-509, c.29, c.74) affecting TGF beta 1 secretion and a deletion (c.69_77del9) in TGF beta R1 influencing TGF beta 1 signaling were genotyped in 250 healthy individuals. TGF beta 1 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, TGF beta 1 levels were obtained for 17 individuals. Mean TGF beta 1 levels were 1046.2 pg, 566.7 pg. 740.6 pg, 1001.8 pg. 701.2 pg and 2844 pg 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 TGF beta 1/TGF beta R1 on secreted TGF beta 1 levels in vitro could not be clarified. The inter-individual variation in TGF beta 1 levels for individuals with the same genotype was too large to obtain statistically significant differences among genotypes.
- 出版日期2010-4
