Plasma level of TGF beta 1 is associated with the polymorphism rs1800469 of the TGFB1 gene in pediatric liver recipients
Rivada М. Kurabekova1, Olga М. Tsirulnikova1,2, Irina E. Pashkova1, Olga E. Gichkun1,2, Galina A. Olefirenko1, Olga P. Shevchenko1,2, Artem R. Monakhov 1, Sergey V. Gautier 1,2.
1Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Introduction: Investigation of new prognostic biomarkers for posttransplant complications is an important issue in today’s transplantology. It has been shown that the blood plasma level of transforming growth factor β1 (TGFβ1) may correlate with graft dysfunction development in pediatric liver recipients. However, it is unknown whether these associations are causal and which factors can determine the cytokine plasma levels. The aim was to access the relations of TGFβ1 blood plasma concentrations before and after liver transplantation (LT) with TGFB1 gene polymorphism in pediatric recipients.
Materials: 136 children (62 boys) with LT; aged from 3 to 192 (median - 11) months and 64 healthy donors (27 men) aged from 27 to 64 (median - 31) years were included in the study. Concentrations of TGFβ1 were measured in blood plasma before, one month and one year after LT by ELISA. The three types (rs1800469, rs1800470 and rs1800471) of single nucleotide polymorphism (SNP) of TGFB1 was studied by TaqMan SNP genotyping assay.
Results: In the liver recipients, the median level of TGF-β1 was 4.17 (1.28-9.29), 6.25 (1.35–15.52) and 7.57 (1.86–13.50) ng/ml before, one month and one year after LT, respectively; frequencies of the SNPs: rs1800469 - 21% AA homozygotes, 35% AG heterozygotes, and 44% GG homozygotes; rs1800470 – 77% AA, 15% AG, 7% GG; rs1800471 – 0% GG, 12% GC, 88% CC. In the donors, the median level of TGF-β1 was 6.65 (3.77 – 17.77), the SNPs frequencies: rs1800469 - 15% AA, 34% AG and 51% GG; rs1800470 - 85% AA, 15% AG and 0% GG, and rs1800471 – 0% GG, 6% GC, 94% CC. A comparative analysis reviled that the cytokine level in pts. with GG genotype rs1800469 was significantly higher than with AG: 1.87 (0.60-7.25) vs 5.25 (2.86–9.45), p=0.038. Differences in levels of TGF-β1 in pts. or donors with other SNPs were not found.
Conclusion: Higher plasma level of TGF-β1 may be associated with genotype GG rs1800469 TGFB1 in pediatric liver recipients. Further investigation should be carried out to evaluate whether this polymorphism may impact on posttransplant complications.
