Polymorphisms rs1800469, rs1800471 of the TGFB1 gene detected in patients with chronic heart failure who waiting cardiac transplantation
Olga Gichkun1,2, Rivada Kurabekova1, Olga Shevchenko1,2, Nadegda Koloskova1, Alex Shevchenko1,2.
1Regulatory mechanisms in Transplantology, Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation; 2Department of transplantology and artificial organs, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Introduction: Chronic cardiovascular disease (CVD) is the most common cause of death in many countries around the world. The genetic mechanisms underlying the pathogenesis of CVD are not fully understood. It has been shown that transforming growth factor β1 regulates the production of the intracellular matrix, inhibits the proliferation of vascular smooth muscle cells, disrupts the division and migration of endothelial cells, which can contribute to the development of coronary heart disease. The aim was to estimate the impact of three types of TGFB1 gene polymorphism (rs1800469, rs1800470, rs1800471) in patients with terminal heart failure who waiting cardiac transplantation.
Materials and Methods: The study included 110 patients (99 men; 44±14 years) with heart failure caused by dilated (57 cases) or ischemic (53 cases) cardiomyopathy. The comparison group was healthy blood donors (n=64). Single nucleotide polymorphism (SNP) (rs1800469, rs1800470 and rs1800471) of TGFB1 gene was studied by TaqMan SNP genotyping assay.
Results: The pts. had next frequencies of the investigated alleles: rs1800469 - 20% AA homozygotes, 38% AG heterozygotes, and 42% GG homozygotes; rs1800470 – 83% AA, 13% AG, 4% GG; rs1800471 – 3% GG, 13% GC, 84% CC. The SNPs frequencies in the donors had next profile: rs1800469 - 15% AA, 34% AG and 51% GG; rs1800470 - 85% AA, 15% AG and 0% GG, and rs1800471 – 0% GG, 6% GC, 94% CC. There was deviation from Hardy-Weinberg equilibrium in distribution of SNPs rs1800469 and rs1800470 in cardiac pts. In healthy donors all the investigated SNPs were in Hardy-Weinberg equilibrium. Carriers of the genotype CC (p = 0.037, OR = 0.23, 95% CI: 0.054-1.031) and more often the allele G of rs1800471 (p = 0.037, OR = 4,2, 95% CI: 0.970-18.55) were found in patients less often than in healthy individuals. In patients with ischemic heart disease, the genotype GG was less common (p = 0.035, OR = 2.68, 95% CI: 1.061-6.793) and more often the allele A of rs1800469 (p = 0.035, OR = 0.37 95% CI: 0.148-0.942) than in patients with dilated cardiomyopathy.
Conclusion: The frequency of rs1800471 TGFB1 differs between patients and healthy individuals. Allele A rs1800469 TGFB1 is associated with ischemic heart disease in potential heart transplant candidates.
