Relationship between Epicardial and Coronary Adipose Tissue and the Expression of Adiponectin, Leptin, and Interleukin 6 in Patients with Coronary Artery Disease.

Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest to researchers, owing to their potential effects on the myocardium and blood vessels. The aim of the study was to assess the expression and secretion of adipocytokine genes in the AT of patients with coronary artery disease (CAD) and patients with aortic or mitral valve replacement. This study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous, epicardial (EAT), and perivascular AT (PVAT), and were cultured for 24 h. EAT exhibited the lowest level of adiponectin gene expression and secretion, regardless of nosology, and high expression levels of the leptin gene and interleukin-6 (IL-6). However, EAT adipocytes in patients with CAD were characterized by more pronounced changes in comparison with the group with heart defects. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with CAD. Therefore, our results revealed the pathogenetic significance of alterations in the adipokine and cytokine status of adipocytes of EAT and PVAT in patients with CAD.

DNA excision repair and double-strand break repair gene polymorphisms and the level of chromosome aberration in children with long-term exposure to radon.

PURPOSE: To study polymorphic variants of repair genes in people affected by long-term exposure to radon. The chromosome aberration frequency in peripheral blood lymphocytes was used as the biological marker of genotoxicity. MATERIALS AND METHODS: Genotyping of 12 single nucleotide polymorphisms in DNA repair genes (APE, XRCC1, OGG1, ADPRT, XpC, XpD, XpG, Lig4 and NBS1) was performed in children with long-term resident exposure to radon. Quantification of the aberrations was performed using light microscopy. RESULTS: The total frequency of aberrations was increased in carriers of the G/G genotype for the XpD gene (rs13181) polymorphism in recessive model confirmed by the results of ROC-analysis ('satisfactory predictor', AUC = 0.609). Single chromosome fragments frequency was increased in carriers of the G/G genotype in comparison with the T/T genotype. In respect to the total frequency of aberrations, the G/G genotype for the XpG gene (rs17655) polymorphism was also identified as a 'satisfactory predictor' (AUC = 0.605). Carriers of the T/C genotype for the ADPRT gene (rs1136410) polymorphism were characterized by an increased level of single fragments relative to the T/T genotype. CONCLUSION: The relationships with several types of cytogenetic damage suggest these three SNP (rs13181, rs17655 and rs1136410) may be considered radiosensitivity markers.

Associations of DNA-repair gene polymorphisms with a genetic susceptibility to ionizing radiation in residents of areas with high radon (222Rn) concentration.

PURPOSE: To investigate the individual radiosensitivity of the human genome in long-term residents of areas with high radon concentration. MATERIALS AND METHODS: The materials used for this investigation were venous blood samples extracted from children living in the boarding school of Tashtagol (Kemerovo Region, Russia). Cytogenetic damage assessment was performed using the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes. PCR, gel electrophoresis and product detection using a transilluminator were used to determine polymorphisms in the genes ADPRT (rs 1136410), hOGG1 (rs 1052133), NBS1 (rs 1805794), XRCC1 (rs 25487), XpC (rs 2228001), XpD (rs 13181), and XpG (rs 17655). Statistical analysis was performed using nonparametric methods. To ensure accurate results, FDR-correction for multiple comparisons was performed. RESULTS: We discovered a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN) in carriers of the His/His genotype of the XpG gene Asp1104His polymorphism in comparison to heterozygous and homozygous carriers of the Asp allele. In addition, the Ala/Ala genotype for the ADPRT gene Val762Ala polymorphism and the Glu/Gln genotype for the NBS1 gene Glu185Gln polymorphism were associated with the elevated frequency of binucleated lymphocytes with nucleoplasmic bridges (NPB). CONCLUSIONS: As a result of this study, the elevated frequency of cytogenetic damage in people with particular DNA-repair gene polymorphisms in response to chronic exposure to radon was demonstrated. It was shown that the genes and corresponding polymorphisms (the XpG gene Asp1104His polymorphism, the ADPRT gene Val762Ala polymorphism and the NBS1 gene Glu185Gln polymorphism) can be used as molecular genetic markers of increased individual radiosensitivity in long-term residents of areas with high concentrations of radon.