17 research outputs found
Frequency of hyperglycemia and polymorphism of TNF and TP53 genes in patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer
BACKGROUND: Β«The vicious circleΒ» of associations of diabetes mellitus (DM) with pancreatic pathology, when pancreatic diseases can initiate DM, and type 2 DM β cause functional and organic pancreatic pathology, determines the search for possible associations. Some studies have established a relationship between TNF or TP53 polymorphisms with DM or with pancreatic diseases.AIMS: to determine and compare fasting plasma glucose and the frequency of hyperglycemia in patients with acute pancreatitis (APp), chronic pancreatitis (CPp), pancreatic cancer (PCp) depending on gender, etiology or stage of the disease, polymorphism -308G/A TNF gene in all patients, and polymorphism 72Arg/Pro gene TP53 in PCp..MATERIALS AND METHODS: At the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: frequency of hyperglycemia in APp, CPp, PCp, considering the polymorphism TNF and TP53 genes.Β RESULTS: The lowest age-standardized fasting plasma glucose (FPG) was found in CPp (6,2Β±0,2 mmol/l) than in APp (6,7Β±0,2 mmol/l, p=0,041). In PCp (6,6Β±0,2 mmol/l), the average levels of FPG did not differ substantially when compared with APp (p=0,749) or CPp (p=0,092). In APp, the norm of GP was detected less frequently (31,8%) than in CPp (54,6%, Ο2 =6,3, p=0,012), and the frequency of the norm of GP in PCp (48,9%) did not differ with that in APp or CPp. The frequency of FPGβ₯6,1<7,0 mmol/l did not differ in APp (20,5%), CPp (9,3%) or PCp (17,8%). The frequency of FGPβ₯7.0 mmol/l did not differ in APp CPp and PCp: 47,7, 36,1, 33,3%. Logistic regression analysis revealed a tendency for an increased chance of having stage 3β4 PC with FPGβ₯7,0 mmol/l (Exp (B)=3,205 95%CI 0,866β11,855, p=0,081) in PCp, but not in patients with pancreatic necrosis or βdefiniteΒ» Π‘P.The frequencies of G/G (71,4, 74,7, 76,2%), G/A (26,2, 24,1, 23,8%) of TNF genotypes did not differ in APp, CPp or PCp, p>0,05. In PCp genotypes Arg/Arg, Arg/Pro, Pro/Pro polymorphism gene 72Arg/Pro TP53 in 2,4, 35,7, 61,9% of cases. No associations of GPβ₯7,0 mmol/l with TNF polymorphism in APp, CPp, PCp and with TP53 polymorphism in PCp were obtained.CONCLUSIONS: The frequency of FGPβ₯7,0 mmol/l did not differ for various pancreatic disease and was not associated with the risk of pancreatic necrosis and βdefinedβ CP. The -308G/A polymorphism TNF gene did not differ in APp, CPp or PCp and was not associated with impaired carbohydrate metabolism. The 72Arg/Pro polymorphism TP53 gene in PCp was not associated with impaired carbohydrate metabolism
Molecular genetic markers of myocardial infarction in combination with type 2 diabetes
Aim. To study associations of rs2464196 and rs11212617 polymorphisms with the development of myocardial infarction (MI) in combination with type 2 diabetesΒ (T2D).Material and methods. The study included two groups: main group (n=115) β patients with prior myocardial infarction and T2D, comparisonΒ group (n=116) β patients with myocardialΒ infarction without T2D, hospitalizedΒ from December 1, 2018 to DecemberΒ 31, 2019 at the Regional Vascular Center β 1 of the City Clinical Hospital β 1. Participants were comparable in sex and age. Patients underwentΒ clinical and instrumental investigations,Β a genetic test for single nucleotide polymorphisms, which showed associations with the developmentΒ of MI and T2D according to genome-wideΒ association study (GWAS): rs2464196 of the HNF1AΒ gene, rs11212617 of the ATM gene.Results. Carriage of the AA genotype of the HNF1AΒ rs2464196 polymorphism was found to be associated MI in combination with T2D in the general group (oddsΒ ratio (OR), 3,180, 95% confidence interval (CI), 1,206-8,387, p=0,015). After division of the group by sex, significant differencesΒ remained only in women (OR=9,706, 95% CI, 1,188-79,325, p=0,011).Conclusion. The data obtained can make it possible to identify a priority group of patients for personalized prevention of cardiovascular diseases
Study of the association of rs3746444 of the MIR499A gene and rs6922269 of the MTHFD1L gene with progressive atherosclerosis in patients with coronary heart disease
The aim of the study is to evaluate the association of some molecular genetic markers with progressive atherosclerosis.
Material and methods. In total, the study included 202 patients (147 men and 55 women), who were divided into 2 groups. The 1st (main) group included patients with coronary artery disease (100 people) who had a combination of two or more cardiovascular events during the last 2 years before inclusion: myocardial infarction or unstable angina pectoris, arterial stenting for urgent indications (coronary and peripheral), stroke; acute ischemia, thrombosis or amputation of the lower extremities. The 2nd group (comparisons) included 102 patients with coronary artery disease who did not have any of the above cardiovascular events during the last 2 years before inclusion. DNA was isolated from peripheral blood samples by phenol-chloroform extraction.
Results. In the group with progressive atherosclerosis at the age of 55 years and older, the AA rs3746444 genotype of the MIR499A gene was absent in both men and women, while in the control group its frequency reached 8.3 % (p = 0.044). The odds ratio of detecting the carriage of the heterozygous genotype AG of the rs6922269 polymorphism of the MTHFD1L gene in the group with progressive atherosclerosis is 0.5 times lower compared to the control group (95 % confidence interval 0.3β0.9; p = 0.034).
Conclusions. Carrying the AA genotype rs3746444 of the MIR499A gene is a conditionally protective factor against the development of progressive atherosclerosis at the age of 55 years and older. Carrying the AG genotype of the rs6922269 polymorphism of the MTHFD1L gene is associated with a reduced likelihood of developing progressive atherosclerosis in patients with CAD
ΠΡΡΠΎΡΠΈΠ°ΡΠΈΡ ΠΎΠ΄Π½ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΡΡ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½Π° NOS1AP Ρ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT
Highlights. The association of single nucleotide polymorphic variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval was found in men of the Siberian population.Aim. To study the association of single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene with the duration of the QT interval.Methods. The study sample of men (1353 people) aged 25β69 years was formed from the DNA bank of participants in the international HAPIEE project and screening of young people 25β44 years old, residents of Novosibirsk. From each age subgroup (25β29, 30β34, β¦, 65β69 years old), about 10β15% of men with the shortest, average and longest QT interval were selected and the corresponding groups were formed. Genotyping of rs4657139 was carried out using PCR with RFLP (polymerase chain reaction followed by restriction fragment length polymorphism analysis). Genotyping rs12143842 β using RT-PCR (real-time polymerase chain reaction).Results. At the age of over 50 years, the CC genotype rs12143842 was detected in 66.1% of men in the group with a short and average QT interval and in 50.6% in the group with a long QT interval, while the TT genotype prevailed in the group with a long QT interval, 10, 8% of cases (odds ratio (OR) = 3.345, 95% confidence interval (CI) 1.149β9.739, p = 0.02). The homozygous TT genotype rs4657139 was more common in the long QT group, in 20.1% of cases, while the AA and AT genotypes predominated in the short, average QT groups (p = 0.041). A similar trend persists when separating by age in people over 50 years of age (p = 0.031) and when comparing genotype frequencies in the long and average QT groups in the model TT vs AA + AT & long QT vs short + average QT (p = 0.003).Conclusion. Single nucleotide variants rs12143842 and rs4657139 of the NOS1AP gene are associated with the duration of the QT interval in male residents of Novosibirsk.ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ. Π£ ΠΌΡΠΆΡΠΈΠ½ ΡΠΈΠ±ΠΈΡΡΠΊΠΎΠΉ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π° Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ ΠΎΠ΄Π½ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΡΡ
ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² rs12143842 ΠΈ rs4657139 Π³Π΅Π½Π° NOS1AP Ρ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT.Π¦Π΅Π»Ρ. ΠΠ·ΡΡΠΈΡΡ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ ΠΎΠ΄Π½ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΡΡ
ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² rs12143842 ΠΈ rs4657139 Π³Π΅Π½Π° NOS1AP Ρ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠ°Ρ Π²ΡΠ±ΠΎΡΠΊΠ° ΠΌΡΠΆΡΠΈΠ½ (1 353 ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°) Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 25β69 Π»Π΅Ρ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π° ΠΈΠ· Π±Π°Π½ΠΊΠ° ΠΠΠ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠ² ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΠ΅ΠΊΡΠ° HAPIEE ΠΈ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π° ΠΌΠΎΠ»ΠΎΠ΄ΡΡ
Π»ΡΠ΄Π΅ΠΉ 25β44 Π³ΠΎΠ΄Π°, ΠΆΠΈΡΠ΅Π»Π΅ΠΉ ΠΠΎΠ²ΠΎΡΠΈΠ±ΠΈΡΡΠΊΠ°. ΠΠ· ΠΊΠ°ΠΆΠ΄ΠΎΠΉ Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΠΎΠΉ ΠΏΠΎΠ΄Π³ΡΡΠΏΠΏΡ (25β29, 30β34, β¦, 65β69 Π»Π΅Ρ) ΠΎΡΠΎΠ±ΡΠ°Π½Ρ ΠΎΠΊΠΎΠ»ΠΎ 10β15% ΠΌΡΠΆΡΠΈΠ½ Ρ ΠΊΠΎΡΠΎΡΠΊΠΈΠΌ, ΡΡΠ΅Π΄Π½ΠΈΠΌ ΠΈ Π΄Π»ΠΈΠ½Π½ΡΠΌ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΠΎΠΌ QT ΠΈ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Ρ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠ΅ Π³ΡΡΠΏΠΏΡ. ΠΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ rs4657139 ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° Π΄Π»ΠΈΠ½ ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΎΠ½Π½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ². ΠΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ rs12143842 β Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Π² ΡΠ΅ΠΆΠΈΠΌΠ΅ ΡΠ΅Π°Π»ΡΠ½ΠΎΠ³ΠΎ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΡΡΠ°ΡΡΠ΅ 50 Π»Π΅Ρ Π³Π΅Π½ΠΎΡΠΈΠΏ Π‘Π‘ rs12143842 Π²ΡΡΠ²Π»Π΅Π½ Ρ 66,1% ΠΌΡΠΆΡΠΈΠ½ Π² Π³ΡΡΠΏΠΏΠ΅ ΠΊΠΎΡΠΎΡΠΊΠΎΠ³ΠΎ ΠΈ ΡΡΠ΅Π΄Π½Π΅Π³ΠΎ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT ΠΈ Ρ 50,6% Π² Π³ΡΡΠΏΠΏΠ΅ Π΄Π»ΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QΠ’, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π³Π΅Π½ΠΎΡΠΈΠΏ Π’Π’ ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°Π» Π² Π³ΡΡΠΏΠΏΠ΅ Ρ Π΄Π»ΠΈΠ½Π½ΡΠΌ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΠΎΠΌ QT, 10,8% ΡΠ»ΡΡΠ°Π΅Π² (ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π½ΡΠΎΠ² (ΠΠ¨) 3,345, 95% Π΄ΠΎΠ²Π΅ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π» (ΠΠ) 1,149β9,739, p = 0,02). ΠΠΎΠΌΠΎΠ·ΠΈΠ³ΠΎΡΠ½ΡΠΉ Π³Π΅Π½ΠΎΡΠΈΠΏ Π’Π’ rs4657139 ΡΠ°ΡΠ΅ Π²ΡΡΡΠ΅ΡΠ°Π»ΡΡ Π² Π³ΡΡΠΏΠΏΠ΅ Π΄Π»ΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT, Π² 20,1% ΡΠ»ΡΡΠ°Π΅Π², Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π² Π³ΡΡΠΏΠΏΠ°Ρ
ΠΊΠΎΡΠΎΡΠΊΠΎΠ³ΠΎ, ΡΡΠ΅Π΄Π½Π΅Π³ΠΎ QT ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°Π»ΠΈ Π³Π΅Π½ΠΎΡΠΈΠΏΡ AA ΠΈ AT (p = 0,041). ΠΠ½Π°Π»ΠΎΠ³ΠΈΡΠ½Π°Ρ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΡ ΡΠΎΡ
ΡΠ°Π½ΡΠ»Π°ΡΡ ΠΏΡΠΈ ΡΠ°Π·Π΄Π΅Π»Π΅Π½ΠΈΠΈ ΠΏΠΎ Π²ΠΎΠ·ΡΠ°ΡΡΡ Ρ Π»ΠΈΡ ΡΡΠ°ΡΡΠ΅ 50 Π»Π΅Ρ (p = 0,031) ΠΈ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ ΡΠ°ΡΡΠΎΡ Π³Π΅Π½ΠΎΡΠΈΠΏΠΎΠ² Π² Π³ΡΡΠΏΠΏΠ°Ρ
Π΄Π»ΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΈ ΡΡΠ΅Π΄Π½Π΅Π³ΠΎ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT Π² ΠΌΠΎΠ΄Π΅Π»ΠΈ Π’T vs ΠΠ + ΠΠ’ ΠΈ Π΄Π»ΠΈΠ½Π½ΡΠΉ vs ΠΊΠΎΡΠΎΡΠΊΠΈΠΉ + ΡΡΠ΅Π΄Π½ΠΈΠΉ QT (p = 0,003).ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ΄Π½ΠΎΠ½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΡΠ΅ Π²Π°ΡΠΈΠ°Π½ΡΡ rs12143842 ΠΈ rs4657139 Π³Π΅Π½Π° NOS1AP Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Ρ Ρ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π° QT Ρ ΠΌΡΠΆΡΠΈΠ½, ΠΏΡΠΎΠΆΠΈΠ²Π°ΡΡΠΈΡ
Π² ΠΠΎΠ²ΠΎΡΠΈΠ±ΠΈΡΡΠΊΠ΅
ΠΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π΄ΠΈΡΡΡΠ·Π½ΠΎΠΉ Π-ΠΊΡΡΠΏΠ½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΌΠ΅
Introduction. A more in-depth description of molecular events that disrupt the functioning of the p53 signaling pathway is important for understanding the mechanisms of formation and progression of diffuse B-large cell lymphoma (DCCL), as well as its sensitivity to treatment. The p53 protein exhibits its oncosuppressive function and mediates the antitumor effects of drugs by regulating transcription and/or maturation of a wide range of target genes, including MIR-34A, MIR34B/C, MIR-129-2 and MIR-203. In the tumor tissue of lymphomas, in comparison with normal lymphoid tissue, a decrease in the level of microRNAs encoded by these genes is shown.Aim. The aim of this study was to conduct a comprehensive analysis of the methylation of the genes of the p53-responsive microRNAs MIR-34A, MIR-34B/C, MIR-203 and MIR-129-2, as well as mutations in the DNA-binding domain and destruction of the polyadenylation signal of the TP53 gene in DLBCL.Materials and methods. 136 DNA samples isolated from tumor tissue of patients with DLBCL and 11 DNA samples obtained from lymph nodes with reactive B-cell follicular hyperplasia were analyzed. The methylation status of MIR-203 and MIR-129-2 genes was determined by the method of methyl-specific polymerase chain reaction, MIR-34A and MIR-34B/C genes by the method of methyl-sensitive analysis of high-resolution melting curves. In tumor samples, rs78378222 genotyping was performed by polymerase chain reaction with restriction fragment length polymorphism, resulting in the destruction of the polyadenylation signal, and the nucleotide sequence of the region of the TP53 gene encoding the DNA-binding domain was determined by capillary direct sequencing by Sanger.Results. The methylation detected in lymphoma tissue was tumor-specific. The frequency of analyzed aberrations in the TP53 gene and methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 was 21, 23, 55, 65 and 66 %, respectively. At the same time, methylation of the analyzed genes of p53-responsive microRNAs and aberrations in the TP53 gene in the tumor tissue of patients with DLBCL were independent events with a tendency to mutual exclusion. At the same time, it was shown that in the vast majority of lymphoma samples, the methylation of the MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes was combined.Conclusion. Along with aberrations in TP53, methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes may be an important cause of decreased expression of miR-34a, miR-34b, miR-34c, miR-129 and miR-203 in DLBCL. The combined methylation of the MIR-203, MIR-129-2 and MIR-34B/C genes, as well as the MIR-34B/C and MIR-34A pairs, potentially has a more pronounced pro-tumor effect due to the presence of common targets in the microRNAs encoded by them.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄Π»Ρ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΡ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΠΈ Π΄ΠΈΡΡΡΠ·Π½ΠΎΠΉ Π-ΠΊΡΡΠΏΠ½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΌΡ (ΠΠΠΠΠ), Π° ΡΠ°ΠΊΠΆΠ΅ Π΅Π΅ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΊ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΈΠΌΠ΅Π΅Ρ Π±ΠΎΠ»Π΅Π΅ Π³Π»ΡΠ±ΠΎΠΊΠΎΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΠΎ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΡΠΎΠ±ΡΡΠΈΡΡ
, Π½Π°ΡΡΡΠ°ΡΡΠΈΡ
ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΈ Ρ53. ΠΠ΅Π»ΠΎΠΊ Ρ53 ΠΏΡΠΎΡΠ²Π»ΡΠ΅Ρ ΡΠ²ΠΎΡ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΡ ΠΈ ΠΎΠΏΠΎΡΡΠ΅Π΄ΡΠ΅Ρ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΠΈ/ΠΈΠ»ΠΈ ΡΠΎΠ·ΡΠ΅Π²Π°Π½ΠΈΡ ΡΠΈΡΠΎΠΊΠΎΠ³ΠΎ ΡΠΏΠ΅ΠΊΡΡΠ° Π³Π΅Π½ΠΎΠ²-ΠΌΠΈΡΠ΅Π½Π΅ΠΉ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ MIR-34A, MIR-34B/C, MIR-129-2 ΠΈ MIR-203. Π ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ Π»ΠΈΠΌΡΠΎΠΌ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΡΠΊΠ°Π½ΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ
Π΄Π°Π½Π½ΡΠΌΠΈ Π³Π΅Π½Π°ΠΌΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ MIR-34Π, MIR-34Π/Π‘, MIR-203 ΠΈ MIR-129-2, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² ΠΠΠ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅ΠΌ Π΄ΠΎΠΌΠ΅Π½Π΅ ΠΈ ΡΠ°Π·ΡΡΡΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠΈΠ³Π½Π°Π»Π° ΠΊ ΠΏΠΎΠ»ΠΈΠ°Π΄Π΅Π½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π° Π’Π 53 ΠΏΡΠΈ ΠΠΠΠΠ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ 136 ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΠΠ, Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΈΠ· ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠΠΠ, ΠΈ 11 ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΠΠ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΈΠ· Π»ΠΈΠΌΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ·Π»ΠΎΠ² Ρ ΡΠ΅Π°ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π-ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΎΠ»Π»ΠΈΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π³ΠΈΠΏΠ΅ΡΠΏΠ»Π°Π·ΠΈΠ΅ΠΉ. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΡΠ°ΡΡΡΠ° ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² MIR-203 ΠΈ MIR-129-2 ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ, Π³Π΅Π½ΠΎΠ² MIR-34Π ΠΈ MIR-34Π/Π‘ β ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»-ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΊΡΠΈΠ²ΡΡ
ΠΏΠ»Π°Π²Π»Π΅Π½ΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ. Π ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Ρ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠΎΠΌ Π΄Π»ΠΈΠ½ ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΎΠ½Π½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΎ Π³Π΅Π½ΠΎΡΠΈΠΏΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π°ΡΠΈΠ°Π½ΡΠ° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ rs78378222, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠ°Π·ΡΡΡΠ΅Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»Π° ΠΏΠΎΠ»ΠΈΠ°Π΄Π΅Π½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ, Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΊΠ°ΠΏΠΈΠ»Π»ΡΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΌΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠ°ΠΉΠΎΠ½Π° Π³Π΅Π½Π° Π’Π 53, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΠΠ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠΉ Π΄ΠΎΠΌΠ΅Π½.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ²Π»ΡΠ΅ΠΌΠΎΠ΅ Π² Π»ΠΈΠΌΡΠΎΠΌΠ½ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½ΠΎΡΠΈΠ»ΠΎ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅p. Π§Π°ΡΡΠΎΡΠ° Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ
Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 ΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 21, 23, 55, 65 ΠΈ 66 % ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. ΠΡΠΈ ΡΡΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ
Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠΠΠ ΡΠ²Π»ΡΠ»ΠΈΡΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΌΠΈ ΡΠΎΠ±ΡΡΠΈΡΠΌΠΈ Ρ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΠ΅ΠΉ ΠΊ Π²Π·Π°ΠΈΠΌΠ½ΠΎΠΌΡ ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΈΡ. ΠΠΌΠ΅ΡΡΠ΅ Ρ ΡΠ΅ΠΌ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π² ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡΠ΅ΠΌ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π»ΠΈΠΌΡΠΎΠΌΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 Π½ΠΎΡΠΈΠ»ΠΎ ΡΠΎΡΠ΅ΡΠ°Π½Π½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°ΡΡΠ΄Ρ Ρ Π°Π±Π΅ΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π’Π 53, ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 ΠΌΠΎΠΆΠ΅Ρ ΡΠ²Π»ΡΡΡΡΡ ΡΠ°ΡΡΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ miR-34a, miR-34b, miR-34c, miR-129 ΠΈ miR-203 ΠΏΡΠΈ ΠΠΠΠΠ. Π‘ΠΎΡΠ΅ΡΠ°Π½Π½ΠΎΠ΅ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-203, MIR-129-2 ΠΈ MIR-34B/C, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠ°ΡΡ MIR-34B/C ΠΈ MIR-34A ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΠΈΠΌΠ΅Π΅Ρ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΉ ΠΏΡΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π·Π° ΡΡΠ΅Ρ Π½Π°Π»ΠΈΡΠΈΡ Ρ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ
ΠΈΠΌΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΎΠ±ΡΠΈΡ
ΠΌΠΈΡΠ΅Π½Π΅ΠΉ
ΠΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π³Π΅ΠΌΠΎΠ±Π»Π°ΡΡΠΎΠ·Π°Ρ
The purpose of the study was to present up-to-date data on the frequency and significance of a number of p53-responsive oncosuppressive micrornas genes methylation in malignant neoplasms of the blood system.Material and methods. The search for available literary sources published in the Pubmed and RISC databases was carried out. A total of 399 articles were found, of which 62 were included in this review.Results. The p53 protein regulates a whole class of microRNAs β highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. ΠicroRNAs play an important role in all cellular processes and can have both oncosuppressive and pro-oncogenic properties. Impaired expression of p53-activated oncosuppressive micrornas in various tumors may be associated with specific epigenetic mechanisms (DNA methylation and histone deacetylation). The review examines the molecular and genetic characteristics of oncosuppressive micrornas functioning in normal hematopoiesis, the violation of expression of which is shown in the development of hemoblastoses, namely: miR-34a, miR-34b/c, miR-145, miR-143 and miR-203. It is known that the transcription of the genes of these microRNAs is carried out and regulated from their own promoters. The latest published research results on the diagnostic, prognostic and clinical significance of gene methylation of the microRNAs under consideration in malignant neoplasms of the blood system are presented. According to literature data, common targets for mir-34a, mir-34b/c, mir-145, mir-143 and miR-203 microRNAs are mRNAs of a number of pro-oncogenes, namely: transcription factor C-MYC, positive cell cycle regulators at the G1/S transition point of CDK4, CDK6 and CYCLIN-D1 phases, anti-apoptotic proteins MDM2, MDM4, BCL2 and MCL1, as well as DNMT3A and DNMT3B methyltransferases and other molecules. In this regard, it should be noted that there are positive feedbacks between p53 and microRNAs activated by it, as well as negative feedbacks between p53-responsive micrornas and C-MYC and DNA methyltransferases.Conclusion. Thus, the data presented in the review clarify the current understanding of the work of the regulatory network of the p53 protein and the micrornas activated by it, and also emphasize the functional association of p53-responsive microRNAs.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠ°ΡΡΠΎΡΠ΅ ΠΈ Π·Π½Π°ΡΠ΅Π½ΠΈΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΡΠ΄Π° Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ
ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ
ΡΠΈΡΡΠ΅ΠΌΡ ΠΊΡΠΎΠ²ΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΏΠΎΠΈΡΠΊ Π΄ΠΎΡΡΡΠΏΠ½ΡΡ
Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΡ
Π² Π±Π°Π·Π°Ρ
Π΄Π°Π½Π½ΡΡ
Pubmed ΠΈ Π ΠΠΠ¦. ΠΠ°ΠΉΠ΄Π΅Π½ΠΎ 399 ΡΡΠ°ΡΠ΅ΠΉ, ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
62 Π±ΡΠ»ΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ Π² Π΄Π°Π½Π½ΡΠΉ ΠΎΠ±Π·ΠΎΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ΅Π»ΠΎΠΊ Ρ53 ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅Ρ ΡΠ΅Π»ΡΠΉ ΠΊΠ»Π°ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ β Π²ΡΡΠΎΠΊΠΎΠΊΠΎΠ½ΡΠ΅ΡΠ²Π°ΡΠΈΠ²Π½ΡΡ
ΠΌΠ°Π»ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ» Π ΠΠ, ΠΊΠΎΡΠΎΡΡΠ΅ Π²Π»ΠΈΡΡΡ Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Π³Π΅Π½ΠΎΠ² Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΠΏΡΡΠ΅ΠΌ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ ΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ. ΠΠΈΠΊΡΠΎΠ ΠΠ ΠΈΠ³ΡΠ°ΡΡ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π²ΠΎ Π²ΡΠ΅Ρ
ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ
ΠΈ ΠΌΠΎΠ³ΡΡ ΠΈΠΌΠ΅ΡΡ ΠΊΠ°ΠΊ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΠ΅, ΡΠ°ΠΊ ΠΈ ΠΏΡΠΎΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π½ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΡ
Ρ53 ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»ΡΡ
ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΡΠ²ΡΠ·Π°Π½Ρ ΡΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ (ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΠΠ ΠΈ Π΄Π΅Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π³ΠΈΡΡΠΎΠ½ΠΎΠ²). Π ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ, ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΡΡΡΠΈΡ
ΠΏΡΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΌ ΠΊΡΠΎΠ²Π΅ΡΠ²ΠΎΡΠ΅Π½ΠΈΠΈ, Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΊΠΎΡΠΎΡΡΡ
ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π³Π΅ΠΌΠΎΠ±Π»Π°ΡΡΠΎΠ·ΠΎΠ², Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: miR-34a, miR-34b/Ρ, miR-145, miR-143 ΠΈ miR-203. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΡΠΈΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈ ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅ΡΡΡ Ρ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ². ΠΡΠΈΠ²Π΅Π΄Π΅Π½Ρ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ, ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌΡ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΠΌΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡΡ
ΡΠΈΡΡΠ΅ΠΌΡ ΠΊΡΠΎΠ²ΠΈ. Π‘ΠΎΠ³Π»Π°ΡΠ½ΠΎ Π΄Π°Π½Π½ΡΠΌ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΡΠ°ΡΡΡΠΌΠΈ ΠΎΠ±ΡΠΈΠΌΠΈ ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ Π΄Π»Ρ ΠΌΠΈΠΊΡΠΎΠ ΠΠ miR-34a, miR-34b/Ρ, miR-145, miR-143 ΠΈ miR-203 ΡΠ²Π»ΡΡΡΡΡ ΠΌ-Π ΠΠ ΡΡΠ΄Π° ΠΏΡΠΎΠΎΠ½ΠΎΠΊΠΎΠ³Π΅Π½ΠΎΠ², Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° C-MYC, ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π° Π² ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΠΎΠΉ ΡΠΎΡΠΊΠ΅ ΠΏΠ΅ΡΠ΅Ρ
ΠΎΠ΄Π° G1/S ΡΠ°Π· CDK4, CDK6 ΠΈ CYCLIN-D1, Π°Π½ΡΠΈΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ² MDM2, MDM4, ΠCL2 ΠΈ MCL1, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΠΠ-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π· DNMT3A ΠΈ DNMT3B ΠΈ Π΄ΡΡΠ³ΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ». ΠΠΏΠΈΡΠ°Π½ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΎΠ±ΡΠ°ΡΠ½ΡΡ
ΡΠ²ΡΠ·Π΅ΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Ρ53 ΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠΌΠΈ ΠΈΠΌ ΠΌΠΈΠΊΡΠΎΠ ΠΠ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ
ΠΎΠ±ΡΠ°ΡΠ½ΡΡ
ΡΠ²ΡΠ·Π΅ΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΠΌΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ c-MYC ΠΈ ΠΠΠ-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·Π°ΠΌΠΈ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°Π½Π½ΡΠ΅, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠ΅ Π² ΠΎΠ±Π·ΠΎΡΠ΅, ΡΡΠΎΡΠ½ΡΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΡ ΠΎ ΡΠ°Π±ΠΎΡΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠΉ ΡΠ΅ΡΠΈ Π±Π΅Π»ΠΊΠ° Ρ53 ΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΡ
ΠΈΠΌ ΠΌΠΈΠΊΡΠΎΠ ΠΠ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ΄ΡΠ΅ΡΠΊΠΈΠ²Π°ΡΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ
NUMBER OF COPIES OF MITOCHONDRIAL DNA OF LEUKOCYTES AS A MARKER OF PREDISPOSITION TO CORONARY HEART DISEASE AND SUDDEN CARDIAC DEATH
The review provides information on studies that have studied the relationship between the number of copies of mitochondrial DNA (mtDNA) in peripheral blood leukocytes with coronary heart disease and sudden cardiac death (SCD). Mitochondrial dysfunction is a major component of the aging process and can play a key role in the development of cardiovascular diseases of atherosclerotic origin, and the number of copies of mtDNA is an indirect biomarker of mitochondrial function. According to a number of studies, measuring the number of copies of mtDNA in peripheral blood leukocytes can improve the risk assessment of CVD to decide on the beginning of primary prevention of CVD. So far, relatively few such studies have been carried out. Nevertheless, the results obtained, according to the authors, allow us to hope that this indicator can be used in assessing the risk of individual CVD. Further studies carried out on large groups in a prospective design should provide the necessary additional information on the feasibility of including this indicator in the appropriate risk meters
Association of SCN5A gene polymorphism with dilated cardiomyopathy
Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7Β±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7Β±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6Β±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele β 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the Π allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men