Association of plasma TGF-β1 levels with polymorphic loci and TGFB1 haplotypes rs1800469 and rs1800470 in pediatric liver transplant recipients

Objective: to investigate the association between plasma TGF-β1 levels in pediatric liver transplant (LT) recipients, both preand post-transplantation, and the polymorphic alleles and haplotypes at rs1800469 and rs1800470 loci of the TGFB1 gene. Materials and methods. The study cohort comprised 135 pediatric LT recipients, aged 3 to 98.4 months (mean age 8.2 years, median 8 months). The control group consisted of 77 healthy individuals, aged 30.3 ± 5.2 years. Plasma TGF-β1 levels were quantified using ELISA. Genomic DNA from participants was analyzed for the polymorphic loci rs1800469 and rs1800470 of the TGFB1 gene using real-time polymerase chain reaction PCR with TaqMan probes. Results. Blood TGF-β1 level in pediatric LT recipients pre-transplant was 4.6 (1.1–9.5) ng/mL. One month post-transplant, cytokine level increased to 6.3 (1.7–15.0) ng/mL (p = 0.008), and after one year, it rose further to 7.0 (1.9–13.5) ng/mL (p = 0.0001). Healthy adults had significantly higher TGF-β1 levels, with a median of 11.7 (6.4–16.9) ng/mL (p = 0.0000), compared to pediatric recipients. The distribution frequencies of the rs1800469 and rs1800470 polymorphic alleles in pediatric LT recipients did not significantly differ from those in healthy individuals. However, the occurrence of rare haplotypes (T-T and C-C) was significantly higher in pediatric recipients. Before transplantation and 1 month after the procedure, TGF-β1 levels in pediatric recipients were not associated with the carriage of the studied alleles or haplotypes. However, at 1-year post-transplant, higher TGF-β1 levels in pediatric recipients were significantly associated with the major alleles (C/C + C/T) of rs1800469 and the rs1800470 T/T genotype, as well as with the T-T haplotype. In healthy individuals, TGF-β1 levels were not influenced by the rs1800469 and rs1800470 alleles individually, but high cytokine levels were associated with the C-C haplotype. Conclusion. In pediatric LT recipients, elevated TGF-β1 levels at 1-year post-transplant are associated with the presence of the major alleles C (rs1800469) and T (rs1800470), as well as the T-T haplotype of the TGFB1 gene. This suggests that these polymorphic loci may influence the development of post-transplant complications and could potentially serve as biomarkers for predicting clinical outcomes in LT.