It was the purpose of this study to better define the frequency of HLA-B27 subtypes and HLA class II alleles among indigenous populations from the eastern tip of the Chukotka Peninsula of Siberia, Russia, which have higher frequencies of HLA-B27 (40%) and spondyloarthropathies (2%) than Caucasian populations and test the hypothesis that these populations are more closely related to Orientals. Siberian Eskimos and Chukchi residing in four coastal villages on the Chukotka Peninsula inhabited by Siberian Eskimos and Chukchi people were examined using oligotyping of the polymerase-chain reaction-amplified second and third exons of the HLA-B27 gene. HLA-class II alleles (DRB1, DQA1 and DQB1) were similarly determined. Of 88 HLA-B27 positive individuals from these villages, all had HLA-B*2705, including the four patients with Reiter's syndrome and the five ankylosing spondylitis, except one Eskimo control who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. HLA-class II typing in 70 Siberian Eskimos and 71 Siberian coastal Chukchi revealed HLA-DRB1*0401, DRB1*0802, *0901 and *1402 to account for nearly all the DRB1 alleles found in this population, similar to what has been described in Eskimos in Alaska, but different from Chinese or native Americans in the U.S. The overwhelming majority of the individuals examined had HLA-DQB1*0301, similar to what has been observed in Native Americans. The Siberian Eskimos differed from the coastal Chukchi only in the occurrence of HLA-DRB1*0701, DQA1*0201, DQB1*0201 alleles, which occurred only in the former group. These data suggest that the Chukotka population is genetically more closely related to Caucasians and native Americans and less to other Oriental populations.

We aimed to identify bone related markers in the peripheral blood of osteoporotic (OP) patients that pointed toward molecular mechanisms underlying late postmenopausal bone loss. Whole blood from 22 late postmenopausal OP patients and 26 healthy subjects was examined. Bone mineral density (BMD) was measured by DXA. Protein levels of p70-S6K, p21, MMP-9, TGFβ1, and caspase-3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. OP registered by low BMD indices in late postmenopausal patients was associated with a significant upregulation of autophagy protein ULK1, cyclin-dependent kinase inhibitor p21, and metalloproteinase MMP-9 gene expression in the blood compared to the healthy controls and in a significant downregulation of mTOR (mammalian target of rapamycin), RUNX2, and ALPL gene expression, while expression of cathepsin K, caspase-3, transforming growth factor (TGF) β1, interleukin- (IL-) 1β, and tumor necrosis factor α (TNFα) was not significantly affected. We also observed a positive correlation between TGFβ1 and RUNX2 expression and BMD at femoral sites in these patients. Therefore, bone loss in late postmenopausal OP patients is associated with a significant upregulation of survival-related genes (ULK1 and p21) and MMP-9, as well as the downregulation of mTOR and osteoblast differentiation-related genes (RUNX2 and ALPL) in the peripheral blood compared to the healthy controls.

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The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

BackgroundRecent studies report on increased serum levels of C-reactive protein (CRP) in systemic scleroderma (SSc) pts.ObjectivesThe current study was aimed at identifying potential correlations between CRP levels, immunologic SSc phenotypes and CRP rs1205 gene polymorphism in the Russian cohort.Methods92 SSc pts were enrolled in the study. Mean age (± SD) was 49,4±12,6 years, mean (± SD) SSc duration was 11,1±9,0 years, increased CRP levels >5 mg/l were documented in 43% pts. CRP levels were analyzed in the following subgroups: with limited (lcSSc) and diffuse (dcSSC) types, with SSc duration <3 years >3, with or without interstitial lung disease (ILD+) and (ILD-), as well as in subgroups with positive antibody titers to DNA topoisomerase I (ATA+) and antibody to centromeres (ACA+). CRP concentrations were measured with highly sensitive immunoturbidimertry method. Allele-specific real time PCR was used to study CRP rs1205 gene polymorphism.ResultsMean CRP (± SD) level was significantly higher in dcSSc vs lcSSc (11,9±15,5 mg/l; vs 4,7±7,4 mg/l, respectively, p=0,006). Pts with disease duration <3 years had higher mean CRP levels as compared to pts with SSc duration >3 years, although the difference was not significant. In pts with disease duration >3 years mean CRP levels were significantly higher among subjects with dcSSc than lcSSc (11,0±15,5 mg/l vs 4,8±7,7 mg/l, respectively, p=0,027). Mean CRP level was higher in (ATA+) pts than in (ATA-) pts (11,0±15,4 mg/l vs 5,5±13,7 mg/l, respectively, p=0,032). No statistical difference in CRP levels was found between (ILD+) and (ILD-) pts, as well as between (ACA+) and (ACA-) pts.Carriers of rs1205 CC genotype had higher CRP levels than carriers of rs1205 T allele,p=0,087). In pts with SSc duration >3 years and carriers of rs1205 CC genotype mean CRP level was significantly higher than in T-allele carriers (12,0±17,4 mg/l vs 5,4±7,4 mg/l, respectively, p=0,021). Similar trends for CRP levels depending on genotypes were established among (ATA+) pts (16,9±20,1 mg/l and 7,3±10,5 mg/l, respectively, p=0,031).ConclusionsIncreased CRP levels were found almost in 50% of Russian SSc pts. Higher CRP levels were associated with specific clinical and immunological SSc parameters and CRP rs1205 CC genotype, signifying unfavorable prognosis.Disclosure of InterestNone declared

Остеопороз-распространенное заболевание, поражающее одну из трех женщин и одного из 10 мужчин в возрасте после 50 лет, которое характеризуется комбинацией сниженной костной массы скелета и изменениями микроархитектоники кости. Близнецовые и семейные исследования показали, что индивидуальная вариабельность костной массы на 50-80% детерминируется генетическими факторами [1-3]. Вместе с тем, по-видимому, этот эффект обусловлен комбинированным влиянием нескольких генов, каждый из которых вносит лишь незначительный вклад в вариабельность костной массы [4]. Для выявления генов, участвующих в детерминации костной массы, используют два разных подхода: анализ сцепления в семьях и изучение генов-кандидатов в группах больных и контроля. Анализ сцепления наиболее трудоемкий по сравнению с анализом больной-контроль. Трансформирующий фактор роста бета-1 (ТФР-β1) является наиболее частой из 3-х изоформ ТФР-β в сыворотке и костной ткани. ТФР-β1 продуцируется остеобластами как неактивный пропептид, который встраивается во вновь образующийся костный матрикс. В процессе костной резорбции пропептид активируется кислым содержимым зоны резорбции, расположенной под остеокластом. ТФР-β1тормозит активность остеокластов и стимулирует пролиферацию и дифференциацию преостеобластов. Таким образом, эффект ТФР-β1 в костном ремоделирова

Nowadays, when making managerial decisions, specialists are faced with the need to process ever-increasing volumes of information in an increasingly shorter time. The need for the development of a methodology for social forecasting on the basis of detailed development models is growing. Since the basis of the activity of the socio-economic system of any level is an anthropogenic factor, this increases the degree of probability of the implementation of various scenarios. To develop more accurate forecasts, it is necessary to use the tools of the economics of quality standardization, metrology, quality management. Standardization determines the ability to normalize and assess sustainability indicators of development, as well as management methods. Metrology provides uniform methods for measuring these indicators. Based on the received information, quality management systems allow making reliable managerial decisions. The use of tools of the economics of quality is possible at almost all stages of socio-economic modelling. The role of elements of the economics of quality, in particular standardization, is especially growing in the development of the digital economy and “smart cities”, where a complete unification of the formats for accumulating and transmitting information to all users is required.

Background:Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels of serum amyloid A (SAA) protein are predisposing factors for secondary AA amyloidosis. The role of SAA1 gene polymorphisms in AS is not well understood.Objectives:To investigate the association of SAA1 gene polymorphism -13T/C (rs12218) with ankylosing spondylitis and to evaluate the influence of this polymorphism on SAA protein concentration.Methods:123 AS patients (72 males, 51 females; age - M (SD) 37.51 (12.77) years; disease duration - 14.28 (11.22) years; BASDAI – 5.59 (1.13); B27-positive - 111 (90.2%) pts) and 95 gender, age matched healthy individuals (control group) were included in this study. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in AS patients.Results:The distribution of genotypes TT, TC and CC differed statistically between AS and control groups (24.4%, 56.1%, 19.5% and 41.1%, 44.2%, 14.7% respectively, χ 2=6.9, p=0.03).The presence of the C allele was associated with the development of AS (OR=1.55 [CI 1.04-2.33], p=0.03). The SAA1 -13T/C polymorphism tended to be associated with SAA protein value in AS patients: TT+TC genotypes -13.8 mg/l [4.2; 91.0], CC genotype -7.8 mg/l [1.6; 29.6], p=0.07. ESR, CRP and BASDAI values did not correlated with SAA1 - 13T/C polymorphism (p=0.6, p=0.4, p=0.4 respectively).Conclusion:The results of our study demonstrated for the first time that SAA1 gene polymorphism -13T/C (rs12218) is associated with susceptibility to AS. It is also shown that this polymorphism can affect the SAA protein level. Our findings need to be verified in AS patients with high levels of SAA protein in various ethnic and population groups.Disclosure of Interests:None declared