Цель: изучить ассоциации полиморфизма 283 A>G (BsmI) гена VDR с остеопоротическими изменениями в различных участках скелета у женщин в постменопаузальном возрасте. Материалы и методы: обследованы 525 женщин в постменопаузе. Остеоденситометрия выполнялась методом двухэнергетической рентгеновской абсорбциометрии. Полиморфизм 283 A>G (BsmI) гена VDR исследовался методом ПЦР в режиме реального времени. Результаты: установлены корреляционные связи (P<0,05) минеральной плотности поясничных позвонков L1-L4, проксимальных отделов левого и правого бедра, шеек правой и левой бедренных костей, дистального отдела предплечья недоминантной руки с весом женщин (rs от 0,36 до 0,54), индексом массы тела (rs от 0,28 до 0,42), длительностью постменопаузального периода (rs от-0,13 до-0,51). Остеопороз у женщин в области поясничных позвонков L1-L4 имел ассоциации с генотипом GG (Р=0,009) и аллелем G (Р=0,016) полиморфизма 283 A>G (BsmI) гена VDR. Роль полиморфизма 283 A>G (BsmI) в остеопоротических изменениях проксимального отдела бедренных костей и дистального отдела предплечья не установлена (P>0,05). Заключение: полученные данные могут быть использованы для выявления предрасположенности к развитию остеопороза у женщин в постменопаузу и повышения эффективности лечебно-профилактических мероприятий.
История открытия и исследований свойств витамина D (VD) связана с изучением этиологии, патогенеза рахита, а впоследствии и других заболеваний скелета, а также с поиском лечебно-профилактических средств для предупреждения и лечения патологии костной ткани. Краткое клиническое описание рахита было сделано Daniel Whistler еще в 1645 году, а несколько позже, в 1650 году, более полную и детальную картину данного заболевания представил Francis Glisson [6]. Понадобилось более 250 лет, прежде чем была расшифрована этиология рахита. Лишь в начале ХХ века благодаря исследованиям таких ученых, как Е.
Significant successes in the study of physiological and pathophysiological patterns of bone remodeling in recent years have highlighted immune factors important role in bone tissue pathology and significantly revised our ideas about postmenopausal osteoporosis development mechanisms. Advanced osteoimmunology and evidence of immune mechanisms key role in bone remodeling disorders gave us possibility for identification of osteoporosis as chronic immune-mediated disease. Moreover, instead of the term “Osteoporosis”, the term “Immunoporosis” was reasonably used. Bone tissue is constantly in state of continuous renewal (remodeling), which is balanced by formation and resorption processes and is achieved through the coordinated functioning of the three main bone cells types. Constant and active interaction between osteocytes, osteoblasts and osteoclasts is ensured by cytokines (RANKL, osteoprotegerin, macrophage colony-stimulating factor, vascular endothelial growth factor, etc) secretion. Moreover, predominantly, bone remodeling regulation is limited by Osteocyte-Osteoblast-Osteoclast system. With pathological changes in immune reactivity, which may be caused by deficiency of estrogen, vitamin D, calcium, inflammatory diseases, etc., various types of immunocompetent cells are activated. This is accompanied with increased RANKL production by leukocyte cells, which potentiates processes of maturation, differentiation of osteoclasts, and increase in their activity. In addition to RANKL secretion, activated leukocytes, including T lymphocytes, enhance other osteoclastogenic cytokines production. IL-1, IL-6, IL-17, TNF and TGF-β are main mediators of accelerated bone loss in postmenopausal women.
147 women aged 31-47 years with autoimmune thyroiditis were examined. The control group included 63 appar- ently healthy women of the same age without thyroid disease. Using enzyme-linked immunosorbent assay, serum levels of tumor necrosis factor α (TNF-α), interleukins (IL) -1β, -6, -8, -17A, receptor activator of nuclear factor-kappa β ligand (RANKL) and osteoprotegerin (OPG) were determined. The median, interquartile range and Spearman’s rank correlation coefficient were calculated. The Mann-Whitney test was used to compare two independent samples. Autoimmune damage of the thyroid gland was characterized by a significant (p<0,001) increase in the levels of IL-1β and IL-6 against the background of a trend towards an increase of serum IL-17A concentration (p=0,067). At the same time, the values of TNF-α and IL-8 did not differ significantly from those of women in the control group (p=0,166 and p=0,102, respectively). Also, autoimmune thyroiditis in women was accompanied by a significant increase of RANKL concentration (p=0.029), while the OPG content remained at control levels (p=0,988). A regular decrease in the OPG/RANKL ratio was also recorded (p=0,017). The presence of a significant (p<0,05) positive relationship of IL-6 concentrations with TNF-α, IL-8, IL-17A and RANKL values, as well as between RANKL and IL-8 values was established. In addition, the concentration of RANKL was characterized by a direct correlation with the content of the anti-inflammatory mediator OPG. Attention is drawn to the revealed negative correlation between the OPG/RANKL index and IL-6 values. Autoimmune thyroiditis in women is characterized by a significant increase of serum levels of IL-1β, IL-6, RANKL and a decrease in the OPG/RANKL index, while the indices of IL-8, TNF-α and OPG production do not change signifi- cantly. For IL-6 concentrations, a positive correlation was established with the values of TNF-α, IL-8, IL-17 and nega- tive - with the OPG/RANKL ratio. RANKL values have a direct relationship with IL-6, IL-8 and OPG levels.
УДК 618.173:616.71-007.234]+615.356:575 зепама в лекарственных формах нами предложен метод высокоэффективной жидкостной хроматогра-фии с УФ-детекцией при определенных условиях. ПОКАЗАÒЕЛИ ДЕНСИÒОМЕÒРИИ КОСÒНОЙ ÒКАНИ У ЖЕНЩИН Â ПОСÒМЕНОПАУЗАЛЬНОМ ÂОЗРАСÒЕ Â ЗАÂИСИМОСÒИ ОÒ ПОЛИМОРФИЗМА RS9594738 (C>T) ГЕНА TNFSF11Кафедра клинической иммунологии, аллергологии и эндокринологии Донецкого национального медицинского университета им. М. Горького, 283003, г. Донецк, пр. Ильича, 16; тел. +38-095-578-72-27. E-mail: mea095@yandex.ru Изучены показатели минеральной плотности костной ткани различных участков скелета у 483 женщин пост-менопаузального возраста в зависимости от генотипа полиморфизма rs9594738 (C>T) гена TNFSF11. Установ-лено, что женщины, имеющие генотипы СТ и ТТ, по сравнению с обладателями генотипа СС, характеризуются существенно сниженными (Р<0,001 -P=0,026) показателями денситометрии в зоне поясничных позвонков L1-L4, проксимальных отделов левой и правой бедренных костей, в том числе шеек левого и правого бедра, а также дис-тального отдела костей предплечья. Результаты исследования могут быть использованы при разработке критериев для выявления предрасположенности к развитию постменопаузального остеопороза и повышения эффективности лечебно-профилактических мероприятий.Ключевые слова: ген TNFSF11, rs9594738, женщины, постменопауза, остеопороз. Immunology, Allergology and Endocrinology Donetsk National Medical University named after M. Gorky, 283003, Donetsk, Illicha Ave., 16; tel. +38-095-578-72-27. E-mail: mea095@yandex.ru Indexes of bone tissue mineral density of various sites of skeleton at 483 postmenopausal women depending on genotype of TNFSF11 gene rs9594738 (C>T) polymorphism were studied. It was established that women, who had CT and a TT genotypes in comparison with CC genotype owners were characterized by significantly lowered (Р<0,001 -P=0,026) densitometry indexes in zone of L1-L4 lumbar vertebrae, left and right proximal femoral departments, including left and right femoral necks, and also forearm bones distal department. Results of this research can be used for development of E. A. MAYLYAN BONE DENSITOMETRY INDICATORS IN POSTMENOPAUSAL WOMEN DEPENDING ON TNFSF11 GENE RS9594738 (C>T) POLYMORPHISM Department of Clinical
Pharmacogenetic testing, that is promising technology for personalized medicine, is already being introduced into clinical practice. Pharmacogenetic approach is especially necessary when prescribing treatment for patients with osteoporosis, because anti-osteoporotic drugs effect can be assessed only after 12 months or more after therapy start. On this basis, aim of study was to estimate alendronic acid effectiveness in women with postmenopausal osteoporosis depending on rs2234693 polymorphism of estrogen receptor type 1 gene (ESR1). Material and methods. 136 patients were included to research. The studies in women were performed twice - before and 12 months after osteoporosis treatment, that included alendronic acid standard doses. Evaluation of 12-month therapy effectiveness was carried out according to bone mineral density increase based on X-ray osteodensitometry. Genotype of rs2234693 polymorphism of ESR1 gene was determined by real-time PCR. Results. Women with postmenopausal osteoporosis after alendronic acid 12-month course demonstrated significant (p<0.001) mineral density increase in various parts of skeleton - lumbar vertebrae L1-L4 (4.26% [1.00; 6.95]), left proximal region and femoral neck (2.76% [0.00; 5.95] and 2.42% [-1.41; 5.53], respectively) and right ones (3.76%[-0.20; 6.65] and 3.27% [0.00; 7.18], respectively). Patients with TT genotype of ESR1 gene rs2234693 polymorphism had lower (p<0.05) increase in mineral density of lumbar vertebrae L1-L4 (2.53% [-0.28; 5.54]) compared to all other patients (4.71% [1.75; 8.08]) or to women with CC genotype (5.52% [1.66; 9.12]). Conclusion. rs2234693 polymorphism of ESR1 gene testing in patients with postmenopausal osteoporosis before antiosteoporotic drugs prescription should be used for individualization of treatment regimens and therapy effectiveness enhancement.
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