Analysis of the Association between the Tgfb1 Gene Haplotype and Liver Diseases in Children.

Transforming growth factor-ß1 (TGF-ß1), a cytokine with immunosuppressive and pro-fibrogenic activity, is a potential marker of infection, liver transplant rejection, and fibrosis. Its levels in the blood and tissues depend on many factors; however, the role of gene polymorphism is still unclear. In this work, the distribution frequency of three single nucleotide polymorphism (SNP) variants of the Tgfb1 gene, namely rs1800469, rs1800470, and rs1800471, was studied in children with end-stage liver disease (ESLD). The study included 225 pediatric liver recipients aged 1 month to 16 years (median, 8 months), including 100 boys and 125 girls, and 198 healthy individuals aged 32.7 ± 9.6 years, including 78 men and 120 women. The indication for liver transplantation in children was ESLD, which was mostly caused by congenital and inherited liver diseases. SNPs were detected by real-time polymerase chain reaction using TaqMan probes and DNA isolated from peripheral blood. SNP frequency distribution was in Hardy-Weinberg equilibrium and did not differ between children with liver diseases and the healthy ones. Analysis of the SNPs frequency based on allelic interaction models did not reveal any differences between patients and the healthy individuals. Evaluation of linkage disequilibrium for Tgfb1 polymorphic variant pairs revealed a statistically significant linkage between all studied variants. Seven haplotypes, which are variants of SNP combinations, were observed in the studied groups of patients and healthy individuals. A total of 80% of the group had three haplotypes, whose frequencies did not differ between patients and the healthy individuals. Significant differences were found in the frequency of the haplotypes A-A-C, G-G-C, and G-A-G (at rs1800469, rs1800470, and rs1800471, respectively), which were observed up to 11 times more often in recipients compared to the healthy individuals. It is possible that these haplotypes are ESLD-predisposing variants, which may also contribute to the development of complications after liver transplantation in children.

The rs1800470 Polymorphism of the TGFB1 Gene Is Associated with Myocardial Fibrosis in Heart Transplant Recipients.

The transforming growth factor ß1 (TGFß1), whose level may depend on the polymorphism of the TGFB1 gene, is involved in the formation of myocardial fibrosis. Myocardial fibrosis in a cardiac allograft may lead to a heart's structural and functional remodeling and subsequent dysfunction. The frequency of occurrence of alleles and genotypes of the TGFB1 gene polymorphic regions rs1800469, rs1800470, and rs1800471 in heart transplant recipients and their association with graft myocardial fibrosis were analyzed. Carriers of the CC genotype (p = 0.023, OR = 0.12, 95% CI: 0.017-1.0), and more often the G allele of rs1800471 (p = 0.023, OR = 7.76, 95% CI: 1.0-60.20), were found among heart transplant recipients less frequently than among healthy individuals. In patients with ischemic heart disease (IHD), the GG genotype was less common (p = 0.035, OR = 2.68, 95% CI: 1.061-6.793), while the A allele of rs1800469 was found more frequently (p = 0.035, OR = 0.37 95% CI: 0.148-0.942) than in patients with dilated cardiomyopathy (DCM). In heart transplant recipients with the AA genotype of rs1800470, myocardial fibrosis, verified by endomyocardial biopsy, was detected more often than in carriers of the G allele (OR = 10.4, 95% CI: 1.152-94.538, p = 0.013). The revealed differences suggest a relationship between TGFB1 gene polymorphism and graft myocardial fibrosis. Studies on a larger group of patients would make it possible to characterize the influence of genetic factors on the formation of myocardial fibrosis in heart transplant recipients.

[MicroRNAs: a role in the development of cardiovascular disease, the possibility for clinical application.]

This review summarizes the published literature devoted to the analysis of diagnostic role of microRNAs in cardiovascular disease. MicroRNAs are a class of small non-coding RNAs that regulate gene expression and affect various cellular functions. Modern methods for the detection of microRNA are described. The data of variations in their concentration in ischemic heart disease, heart failure and other diseases are analyzed. At present, the accumulation of clinical data on the role of these biomarkers will allow to determine the diagnostic and prognostic significance of microRNAs (microRNA sets) in cardiovascular diseases.

[The analysis of relationship between numbers of hemopoietic hematoblasts and laboratory indicators of state of hepatobiliary system in children with congenital and hereditary diseases of liver].

The content of CD34/CD45dim-positive cells in peripheral blood of children with congenital and hereditary diseases of hepatobiliary system is studied. The analysis of relationship between numbers of studied cells and level of C-reactive protein, sCD40L, sCD30 and laboratory parameters specific to liver functions is applied The number of CD34-positive hemopoietic hematoblasts in children with hepatocirrhosis correlated with the level of C-reactive protein, albumin, hemoglobin concentration and quantity of blood erythrocytes. No relationship was established with the levels of sDC40L and sDC30. The number ofstudied cells in children with liver diseases was higher than in healthy adult donors.