Cleavage positions of Bst API, a new restriction endonuclease (ENase) that recognizes palindromic interrupted DNA sequence, have been determined. Recognition sequences and cleavage sites comparison shows that Bst API shares similarity with a number of type II restriction enzymes.

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Финансирование. Исследование не имело спонсорской поддержки. Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов. Для корреспонденции Шевченко Алла Владимировнадоктор биологических наук, ведущий научный сотрудник лаборатории клинической иммуногенетики НИИ клинической и экспериментальной лимфологиифилиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения РАН»,

Among the reasons of primary lymphedema development, a certain role belongs to genetic factors. The specific molecular products participate in remodeling of blood and lymphatic vascular networks. Vascular endothelial growth factors (VEGFs) are key regulators of endothelial functions of the cells, which are responsible for lympho- and vasculogenesis. Moreover, matrix metalloproteinases (ММР) may act as regulators of both lymphangiogenesis, and angiogenesis. Since the regulatory regions of VEGFA gene, as well as of ММР genes are polymorphic, one may suggest, that their different expression level, determined by these polymorphisms, could be associated with development of swellings typical for lymphedema.We have analyzed gene polymorphisms in two regulatory regions of vascular endothelial growth factor-A VEGF-A (rs 699947 and rs 3025039), and matrix metalloproteinase genes MMP2 (rs 2438650), MMP3 (rs 3025058), MMP9 (rs 3918242), and their combinations in the patients with primary lymphedema.A group of patients with primary lymphedema included 72 subjects (55 women and 17 men) at the age of 18 to 81 years. Control group included 526 inhabitants of Novosibirsk (153 men, 373 women) without chronic diseases, comparable for age with lymphedema patients. We have performed typing of regulatory regions in VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 genes (rs 3918242). Fifteen complex genotypes have been revealed that were positively associated with disease. Analysis of the gene network topology has outlined the main intergenic interactions upon primary lymphedema development. MMP2 -1306 CC, MMP9 -1562CC and VEGF +936CC arrange the basic knots in the gene network (53% of total interactions). A number of significantly different complex genotypes was revealed at patients with primary lymphedema with normal body mass index (BMI < 25) and obesity (BMI < 30). Hence, frequency of complex genotype VEGF +936 CC: MMP3 -1171 5А6А:MMP9 -1562 CC in the patients with obesity is increased more 5.5-fold compared to the patients with normal BMI.The data obtained may presume a certain value of the analyzed gene polymorphisms in pathogenesis of primary lymphedema. Topological analysis of gene networks allows to study the structural and functional organization of gene-gene interactions for development of approaches to individyal preventive maintenance and therapy of the disease.

Violation of the extracellular matrix components synthesis regulation contributes to the formation and growth of uterine fbroids (MM). Changes of collagen metabolism in connective tissue may be associated with polymorphism of matrix metalloproteinase (MMP) genes. Aim of the study was to analyze of the association of regulatory regions of matrix metalloproteinase genes MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) with the development of uterine myoma, its histological form, several concomitant gynecological diseases. Material and methods. The clinical study of 69 patients (23–54 years old) with uterine myoma was conducted. According to the anamnesis, 57.9 % of patients had childbirth, 46.4 % of women had an artifcial termination of pregnancy, and 15.9 % of women had endometriosis. In histological examination, in 48.14 % the nodes corresponded to the phenotype of simple fbroids with a large proportion of fbrous tissue, 51.6 % with the phenotype of proliferating fbroids. The comparison group is represented by a random population sample of women from Western Siberia. 183 women without pronounced gynecological pathologies were examined. MMP2-1306 C/T polymorphism was analyzed by TaqMan, MMP3-1171 5A/6A, MMP9-1562 C/T by restriction fragment length polymorphism method. Results. The genotype frequencies of the analyzed genes did not signifcantly differ between the groups. The complex genotype MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT was decreased in women with uterine myoma relative to the persons of the comparison group. In endometriosis patients MMP9-1562CC genotype was reduced and heterozygosity was increased relative to patients without endometriosis. The frequency of MMP2-1306CC:MMP9-1562CT complex genotype is signifcantly higher in women who gave birth than in women who did not give birth. Complex genotypes differences between histological variants of uterine myoma were revealed. Conclusions. The results of the study show the signifcance of polymorphism effect of the regulatory regions of the MMP genes in the development and nature of the course of uterine myoma.

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The endothelial NO synthase (eNOS) and vascular endothelial growth factor (VEGF) imbalance and the polymorphism of these genes may be the predisposition for diabetic retinopathy (DR) development and progression.The aim: to analyze VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes polymorphism and their combinations in patients with type 2 diabetes mellitus (DM2) with and without initial non-proliferative DR.Materials and methods. The study included 200 patients with type 2 diabetes (155 women and 45 men, age – 43–70 years): 111 people without and 89 people with DR. The polymorphism of the regulatory regions of VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes was studied using restriction fragment length polymorphism analysis and TaqMan Real-Time PCR by. Statistical processing was carried out using the software packages Statistica 10.0, SPSS Statistics 23 and the package of original programs for volumetric processing of bioinformation.Results. The VEGF-2578 heterozygosity and two complex genotypes – VEGF-2578CA:VEGF+936CC and NOS3-786CT:VEGF-2578CA:VEGF+936CC – signifi cantly decreased in patients with DR. The predisposition to early DR development to minor genotype of eNOS gene in the NOS3-786CC:VEGF+936CT complex and signifi cantly decreased the homozygous wild-type eNOS genotype in DM2 patients with ophthalmopathology were shown. NOS3-86TT:VEGF2578AA genotype signifi cantly decreased in group with retinopathy developing and the glycated hemoglobin high level.Conclusion. Along with the clinical risk factors for the development of DR in DM2, the genetic polymorphism of the regulatory regions of the genes analyzed by us has a signifi cant weight. When analyzing potential genetic markers, it is important to consider possible joint epistatic/hypostatic effects. The complex analysis of polymorphic gene can help early prognosis of the DR development.

Комбинации полиморфизмов гена фактора роста сосудистого эндотелия и генов его рецепторов (VEGF/VEGFR) в оценке сердечно-сосудистого риска у пациентов с ревматоидным артритомНаучно-исследовательский институт клинической и экспериментальной лимфологии -филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», 630060, г. Новосибирск, Российская Федерация Резюме Введение. Риск развития сердечно-сосудистых осложнений у пациентов с ревматоидным артритом (РА) значительно повышен. Основные факторы развития сердечнососудистого риска (ССР) данный феномен полностью объяснить не могут, поэтому анализируются и особенности системных воспалительных процессов, характерных для РА. Один из важных факторов иммунопатогенеза РА -нарушение синовиального ангиогенеза, которому могут способствовать особенности ангиогенной передачи сигналов, в том числе между фактором роста эндотелия сосудов VEGF и системой его рецепторов VEGFR.Цель исследования -анализ однонуклеотидных полиморфизмов гена VEGF (rs699947, rs3025039), его рецепторов -KDR (rs10020464, rs11133360), NRP-2 (rs849530, rs849563, rs16837641) -и их комбинированной ассоциированности с повышенным ССР у пациентов с РА.Материал и методы. Обследованы 135 пациентов с РА (медиана возраста -55 лет, длительности заболевания -7 лет).Увеличение ССР выявлено у 45,2 % пациентов. Генотипирование осуществляли с использованием методов рестриктного анализа продуктов амплификации и полимеразной цепной реакции в реальном времени (ПЦР-РВ) с использованием TaqMan-зондов.Результаты. Выявлены комплексные генотипы, частота которых повышена в группе пациентов с увеличением ССР относительно пациентов с РА с низким ССР. Наибольшая вероятность формирования высокого ССР выявлена у носителей комплекса KDR 14011TT:NRP2 13581TT:VEGF-2578CC, а раннего проявления высокого ССР -у пациентов с генетическим комплексом KDR 17693CC:KDR 14011TC:NRP2 13581TT:VEGF-2578CA: VEGF+936CC. Выявлены и протективные генотипы у пациентов, которые обладают низким ССР даже при длительном течении РА.Заключение. Полиморфные позиции генов медиаторов ангиогенеза синергично могут быть ассоциированы с определенным ССР у пациентов с РА.