Models, mechanisms & therapies

Monday September 12, 2022 from 17:35 to 18:35

Room: CF-7

246.4 Myocardial fibrosis in heart transplant recipients is associated with the rs1800470 polymorphism of the TGFB1 gene

Olga Gichkun, Russian Federation

Researcher
Regulatory mechanisms in Transplantology
Shumakov National Medical Research Center of Transplantology and Artificial Organs

Abstract

Myocardial fibrosis in heart transplant recipients is associated with the rs1800470 polymorphism of the TGFB1 gene

Olga Gichkun1,2, Olga Shevchenko1,2, Rivada Kurabekova1, Natalia Mozheiko1, Galina Olefirenko1, Nadegda Koloskova1, Alex Shevchenko1,2.

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: Myocardial fibrosis is one of the factors that have a negative impact on long-term prognosis after heart transplantation. Its development is most often accompanied by a violation of the structure and function of the cardiac allograft in recipients. Transforming growth factor β1 is a pleiotropic cytokine involved in the formation of fibrosis. Single nucleotide polymorphisms in the regulatory regions of the TGFB1 gene affect the level of expression and, accordingly, mediate various biological effects of the encoded protein.

The aim: to estimate polymorphisms rs1800469, rs1800470, rs1800471 of the TGFB1 gene and their relationship with myocardial fibrosis in heart transplant recipients.

Materials and Methods: 110 heart transplant recipients were examined, including 99 (84%) men; the average age of the recipients was 44±14 (from 16 to 70) years. Polymorphisms rs1800469, rs1800470, rs1800471 of the TGFB1 gene were determined using real-time polymerase chain reaction (TaqMan probes). Fibrosis of the cardiac allograft was verified by the results of endomyocardial biopsy; thin sections of endomyocardial tissue were stained with Masson's trichrome.

Results: In 49 heart transplant recipients with verified fibrosis, the following distribution of the studied polymorphisms was observed: rs1800469 - 11% AA homozygotes, 35% AG heterozygotes, and 54% GG homozygotes; rs1800470 - 98% AA homozygotes, 2% AG heterozygotes, and 0% GG homozygotes, rs1800471 - 0% GG homozygotes, 2% GC heterozygotes and 98% CC homozygotes. In heart transplant recipients without fibrosis: rs1800469 - 25% AA homozygotes, 46% AG heterozygotes and 29% GG homozygotes, rs1800470 - 82% AA homozygotes, 11% AG heterozygotes, and 7% GG homozygotes, rs1800471 - 100% CC homozygotes. There were no differences in the distribution of genotypes and alleles of polymorphisms rs1800469, rs1800471 of the TGFB1 gene in recipients with and without fibrosis. In heart transplant recipients with the AA genotype of the rs1800470 polymorphism of the TGFB1 gene, myocardial fibrosis was detected more often than in the carriers of the G allele (OR=10.4, 95% CI:1.152-94.538, p=0.013). There were no differences in the distribution of genotypes and alleles of investigated polymorphisms TGFB1 gene in recipients with and without transplant rejection.

Conclusion: The presence of the AA rs1800470 genotype of the TGFB1 gene in heart transplant recipients may be associated with a predisposition to the development of graft myocardial fibrosis.



© 2024 TTS 2022