Increased Frequencies of the ‒174G and ‒572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians.

Abstract-The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants ‒174G/C (rs1800795) and ‒572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the ‒174G and ‒572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

[Social factors of mental health and well-being of older Russians.]

The article highlights social factors of mental health and well-being of older Russians based on the results of wave sociological studies of the perceived quality of life for 2002-2019 and the author's representative survey of older Russians in 2022. Age, gender and employment are the most significant determinants not only of social activity, but also of mental health and emotional well-being. At the same time, the study shows that the pandemic had a multidirectional impact on perceived quality of life among older Russians. Compared to the pre-pandemic situation, after the relaxation of restrictive measures, the parameter of social activity increased significantly, the parameter of mental health remained virtually unchanged, but the emotional problems of elderly Russians became more acute. Due to the severe restrictions for older people, the long period of isolation, and for working pensioners - also due to the need to restructure their work remotely - stress, anxiety and worry have affected everyday life.

[Increased Frequencies of the -174G and -572C IL6 Alleles in Populations of Indigenous Peoples of Siberia Compared to Russians].

The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

TCF7L2 gene polymorphism in populations of f ive Siberian ethnic groups.

Investigation of the frequencies of functionally signif icant gene variants in the context of medical biology and gene geography is a relevant issue for studying the genetic structure of human populations. The transition from a traditional to an urbanized lifestyle leads to a higher incidence of civilizational diseases associated with metabolic disorders, including type 2 diabetes mellitus. The goal of the present paper is to analyze the frequencies of functionally signif icant gene alleles in the metabolic prof iles of indigenous Siberian peoples to identify the gene pool resilience, evaluate the susceptibility of various ethnic groups to metabolic disorders under changing environmental conditions, and predict the epidemiological situation that may occur in the near future. The study was performed in the monoethnic samples of eastern and western Buryats, Teleuts, Dolgans, and two territorial groups of Yakuts. A real-time PCR was used to determine the frequencies of single nucleotide polymorphisms (SNPs) G103894T, rs12255372, and C53341T, rs7903146 in the TCF7L2 gene. The results obtained were compared to the frequencies identif ied for Russians from Eastern Siberia and the values available in the literature. The frequencies of the polymorphic variants studied in the samples from the indigenous Siberian peoples place them in between Caucasian and East Asian populations, following the geographic gradient of polymorphism distribution. A signif icantly lower occurrence of type 2 diabetes risk alleles TCF7L2 (103894T) and TCF7L2 (53341T) in the samples of indigenous Siberian peoples compared to Russians was observed, which agrees with their lower susceptibility to metabolic disorders compared to the newcomer Caucasian population. Taking into account urbanization, a reduced growth in type 2 diabetes incidence may be predicted in indigenous Siberian peoples, i. e. Buryats, Yakuts, Dolgans, and Teleuts, compared to the newcomer Caucasian population. A further study of population structure with respect to different metabolic prof ile genes is required to better understand the molecular genetic foundations of the adaptive potential of indigenous Siberian peoples.

Experiences and Expectations of Ethnic Minorities and Majorities towards Community Pharmacy Medicines-Related Services in Estonia.

The unique professional competence of pharmacists can support the safe and effective use of medicines by patients. Additionally, it is important to acknowledge and incorporate the needs of patients with various cultural and social backgrounds. The objective of this study was to assess and compare the experiences and expectations of Russian- and Estonian-speaking pharmacy customers about medicines-related services in Estonian community pharmacies. Cross-sectional study among pharmacy customers was conducted in Estonia 2018−2020. For data analysis, an Independent t-Test was used to compare experiences and expectations of respondents towards medicines-related services. The study involved 552 pharmacy customers: 58.5% (n = 323) Estonians and 41.5% (n = 229) Russians. The majority of the total sample (78.3%) considered the pharmacist competent to help. Medicines-related concerns were more common among Russians (p = 0.037), however, they sought less contact to consult a pharmacist than Estonians (p < 0.001). Furthermore, expectations about different medicines-related services in the future were higher among Estonians than among Russians (p < 0.001). Community pharmacists in Estonia should focus more on person-centered care to better meet the expectations and needs of different ethnic groups about medicines-related services. It is also important to reduce the language barrier and to increase the recognition of cultural traditions by health professionals.

Origin of the Ukrainian minority of Kazakhstan as inferred from HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes distribution.

The present-day population of Kazakhstan comprises more than 100 ethnic and linguistic groups, of which Ukrainians rates numerically as the fourth, following native Kazakhs, Russians, and Uzbeks. We investigated the HLA profile of Kazakhstani Ukrainians and compared them with those of other populations by applying genetic distances, correspondence analysis, admixture, and haplotype examination. Of the 128 HLA alleles identified, A*02:01 (28.64%), B*07:02 (9.71%), B*13:02 (9.71%), C*06:02 (15.05%), DRB1*07:01 (15.20%), and DQB1*03:01 (24.76%) were the utmost common alleles. The most common 2-locus haplotypes identified were A*02:01 ~ B*13:02 (6.66%), B*13:02 ~ DRB1*07:01 (6.57%), B*13:02 ~ C*06:02 (10.10%), and DRB1*01:01 ~ DQB1*05:01 (12.12%), while A*02:01 ~ B*13:02 ~ C*06:02 ~ DRB1*07:01 ~ DQB1*02:01 were the most frequent five-locus haplotype (4.04%) in Kazakhstani Ukrainians. Comparative analysis revealed that Ukrainians of Kazakhstan are closely related to Eastern Europeans (included Ukrainians), and European Russians, but distant from Asian populations. This supports the historical notion that Kazakhstani Ukrainians originated from Ukraine, following their massive migrations to central Asia in the 18th-20th centuries.

[The dynamics of life-span of citizen of the Russian Federation: the sociological aspect].

The article considers the results of sociological study that was carried out to determine vector of dynamics of indices regulating duration of life of the Russian population, including the expected one. The method of secondary analysis of statistical and sociological information data was applied. Results. Against the background of decreasing of birth rate, "aging of population", migration inflows and transformation of value systems the reduction of population size in The Russian Federation (natural loss) dominates, though life expectancy itself is slightly increasing. The high value of indicator of «death external causes¼ is established. The trend of steady decreasing of infant mortality in Russia over the past 27 years is marked. The groups of factors affecting life expectancy of the Russian population is identified. The main characteristics are revealed that are fundamentally important to ensure higher life expectancy of Russians. One of the demographic behavior models in modern Russia is described. The approaches to solve demographic problems in the Russian Federation, proposed by state bodies on the basis of policy documents (Concept of demographic development of the Russian Federation for the period up to 2025, etc.) are considered. The importance of health-preserving projects (such as "Moscow longevity", etc.), is determined.

Pharmacogenetic testing by polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease patients taking ßß-blockers in the Republic of Sakha (YAKUTIA).

Background The aim of this study was to determine carrier frequencies of the polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease (CHD) patients in Russian and Yakut ethnic groups. The association between the administration of higher doses of bisoprolol and metoprolol and the carriage of these polymorphic markers related to the decreased function of the haplotype of CYP2D6 was also studied. Methods The study included 201 CHD patients (aged 66±8.7 years) receiving metoprolol in titrated dose (12.5-150 mg), bisoprolol (2.5-10 mg) or atenolol (50 mg). Ninety-three patients were Russian (30 men and 63 women), and 108 patients were Yakut (54 men and 54 women). Results In genotyping CHD patients in the Russian and Yakut ethnic groups, there was no significant difference in the prevalence rate of the polymorphic markers G1846A (10.8 vs. 10.2; p=0.871) and C100T (16.1 vs. 16.2; p=1). In patients carrying the polymorphic marker G1846A, the dose of bisoprolol was established to be lower than that in the control group (p=0.0289). Conclusions The carriage frequency of polymorphic markers, which theoretically should differ between Russians and Yakuts as representatives of two different races, in practice turned out to be the same.

Study of the genetic load and diversity of hereditary diseases in the Russian population of the Karachay-Cherkess Republic.

The genetic load and diversity of monogenic hereditary diseases (HD) in the Russian population of Karachay-Cherkess Republic (KCHR), living in 10 administrative and municipal divisions, were studied. The total size of the population surveyed was 410,367 people, including 134,756 Russians. In total, 385 patients from 281 families were registered among Russians of KCHR. Genetic load of AD, AR, and X-linked diseases (3.01 ± 0.32, 1.98 ± 0.26, and 1.23 ± 0.29, respectively) are more than twice higher in cities and municipal centers than in corresponding rural regions (1.00 ± 0.10, 0.89 ± 0.09, and 0.42 ± 0.09, respectively). The diversity of HD was 96 nosological forms: 56 diseases with AD type of inheritance (193 patients from 126 families), 28 clinical forms with AR (152 patients out of 124 families) and 12 diseases with the X-linked type of inheritance (40 affected from 31 families). A comparative analysis of the diversity of AD and AR HD with the previously studied populations and ethnic groups of the European part of Russia (Russians of 7 regions, 5 peoples of the Volga-Ural region, and 5 populations of the North Caucasus) was conducted, showing that Russians in the KCHR preserved genetic load with other Russian populations and its difference from the same mutation pool of Karachays and Circassians.

Serotonergic gene polymorphisms (5-HTTLPR, 5HTR1A, 5HTR2A), and population differences in aggression: traditional (Hadza and Datoga) and industrial (Russians) populations compared.

BACKGROUND: Current knowledge on genetic basis of aggressive behavior is still contradictory. This may be due to the fact that the majority of studies targeting associations between candidate genes and aggression are conducted on industrial societies and mainly dealing with various types of psychopathology and disorders. Because of that, our study was carried on healthy adult individuals of both sex (n = 853). METHODS: Three populations were examined: two traditional (Hadza and Datoga) and one industrial (Russians), and the association of aggression with the following polymorphisms 5-HTTLPR, rs6295 (5HTR1A gene), and rs6311 (5HTR2A gene) were tested. Aggression was measured as total self-ratings on Buss-Perry Aggression Questionnaire. RESULTS: Distributions of allelic frequencies of 5-HTTLPR and 5HTR1A polymorphisms were significantly different among the three populations. Consequently, the association analyses for these two candidate genes were carried out separately for each population, while for the 5HTR2A polymorphism, it was conducted on the pooled data that made possible to introduce ethnic factor in the ANOVA model. The traditional biometrical approach revealed no sex differences in total aggression in all three samples. The three-way ANOVA (µ + 5-HTTLPR + 5HTR1A + 5HTR2A +ε) with measures of self-reported total aggression as dependent variable revealed significant effect of the second serotonin receptor gene polymorphism for the Hadza sample. For the Datoga, the interaction effect between 5-HTTLPR and 5HTR1A was significant. No significant effects of the used polymorphisms were obtained for Russians. The results of two-way ANOVA with ethnicity and the 5HTR2A polymorphism as main effects and their interactions revealed the highly significant effect of ethnicity, 5HTR2A polymorphism, and their interaction on total aggression. CONCLUSIONS: Our data provided obvious confirmation for the necessity to consider the population origin, as well as cultural background of tested individuals, while searching for associations between genes and behavior, and demonstrated the role of cultural attitudes towards the use of in-group aggression. Our data partly explained the reasons for disagreement in results of different teams, searching for candidate-gene associations with behavior without considerations of culturally desirable norms. Previous studies suggested that the 5HTR2A gene polymorphism associates with aggression and criminality. Our data extended these findings, demonstrating the role of rs6311 (5HTR2A gene) in aggression in adult healthy men and women from our samples. We found that G-allele carriers were rated higher on total aggression.

Genome-wide association study in ethnic Russians suggests an association of the MHC class III genomic region with the risk of primary varicose veins.

Heredity is a well-known risk factor for varicose veins, but genetic basis of this condition remains poorly studied. Our aim was to conduct a large-scale genetic association study for primary varicose veins (PVVs) in the population of ethnic Russians. An initial scan using Illumina HumanExome-12 v1.0 BeadChip was performed for 273 patients with PVVs and 250 controls without a history of chronic venous disease and other venous disorders. After quality control and removal of monomorphic markers, 25,424 common and 48,232 rare variants were included in the analysis. 42 single nucleotide polymorphisms (SNPs) were genotyped in the independent replication cohort of 447 PVVs patients and 443 controls. Association of common variants with PVVs was investigated by logistic regression, and the impact of rare variants was analyzed using sequence kernel association test. No effect of low frequency alleles has been revealed in our study. Common variant analysis identified a promising signal at chromosome 6 within classical major histocompatibility complex (MHC) class III subregion. The most strongly associated SNP in a combined analysis that reached a suggestive significance level of 3.2e-05 was polymorphism rs4151657 in the complement factor B gene. Testing for potential pleiotropy with other traits indicated that the same causal variant in this region increases the risk of rheumatoid arthritis and has a negative impact on human height. Our results provide suggestive evidence for the involvement of the MHC class III genes in the pathogenesis of PVVs. Further independent studies are needed to confirm our pilot findings.

Allele rs2010963 C of the VEGFA gene is associated with the decreased risk of primary varicose veins in ethnic Russians.

Objective To study the association of polymorphisms rs699947, rs2010963, rs3025039 in the VEGFA gene region and rs1870377, rs2305949, rs2071559 in the VEGFR2 gene region with the risk of primary varicose veins in ethnic Russians. Methods Genotypes were determined by real-time PCR allelic discrimination. The case group consisted of 448 patients with primary varicose veins and the control group comprised 609 individuals without a history of chronic venous disease. Association was studied by logistic regression analysis. Results Allele rs2010963 C was associated with the decreased risk of varicose veins (additive model of inheritance: odds ratio = 0.73, 95% confidence interval = 0.59-0.91, P = 0.004). Conclusions Our results provide evidence that polymorphism rs2010963 located in the 5' untranslated region of the VEGFA gene can influence genetic susceptibility to primary varicose veins in Russians. Otherwise, it can be in linkage disequilibrium with another functional single nucleotide polymorphism that can alter the level of vascular endothelial growth factor A protein.

Polymorphisms in inflammation-related genes and the risk of primary varicose veins in ethnic Russians.

Inflammation was shown to be activated in varicose veins, although its role in the development of vein wall transformation remains inconclusive. We aimed to investigate the influence of 13 inflammation-related single nucleotide polymorphisms (SNPs) TNF rs1800629 and rs3093661, IL1A rs1800587, IL1RN rs4251961, IL6 rs1800795 and rs1800796, IFNG rs2430561, IL10 rs1800896, TGFB1 rs1800469, HIF1A rs11549465, NFKB1 rs28362491, and rs4648068 on the risk of primary varicose veins (PVVs) in ethnic Russians. We genotyped 709 patients with PVVs and 278 individuals without a history of chronic venous disease and performed a single SNP and a haplotype analysis. Several associations with P < 0.05 were revealed in our study. Variant allele HIF1A rs11549465 T, TNF rs3093661 A, and NFKB1 rs28362491 ATTG deletion showed the reverse association with PVV risk, and allele IL6 rs1800795 C was associated with the increased risk of the studied pathology. Haplotype analysis revealed associations of TNF haplotypes rs3093661 A-rs1800629 G and IL6 rs1800795 C-rs1800796 G with the decreased and the increased risk of PVVs, correspondingly. However, all the observed associations failed to reach statistical significance after the correction for multiple testing, which was set at a level of 10-3 due to many tests performed. Our study therefore provides evidence that investigated polymorphisms do not play a major role in susceptibility to PVVs.

Perfil sociodemográfico e distribuição territorial dos russos em São Paulo: deslocados de guerra da Europa e refugiados da China após a Segunda Guerra Mundial / Social and Professional Profile and Territorial Distribution of Russians in São Paulo: Displaced Persons from Europe and Refugees from China after World War II / Perfil socioprofesional y distribución territorial de los rusos en San Pablo: desplazados de guerra de Europa y refugiados de China tras la Segunda Guerra Mundial

O presente artigo tem por objetivo investigar as principais características de dois grupos de russos vindos ao Estado de São Paulo após a Segunda Guerra Mundial: os deslocados de guerra provenientes dos acampamentos para os deslocados na Europa; e os refugiados russos procedentes da China. Para isso foram realizadas uma sistematização e análise dos dados contidos no banco de dados sobre os deslocados de guerra em São Paulo, consolidado por Salles et al. (2013). A pesquisa revelou que a política brasileira da admissão dos deslocados de guerra enquanto mão de obra industrial teve seu impacto direto no perfil da população russa selecionada para imigrar ao país, que se dirigiu predominantemente à capital paulista. Os refugiados russos da China apresentavam perfil demográfico e social distinto, sendo um grupo com maior parcela de mulheres e crianças e empregado no setor de serviços. As características profissionais dos dois grupos determinaram sua distribuição pelos bairros de São Paulo. Enquanto os deslocados de guerra da Europa se dirigiram para os bairros periféricos e industriais, os russos da China instalaram-se nos bairros mais próximos ao centro da cidade.

The aim of this article is to research the main characteristics of two Russian groups coming to the State of São Paulo after World War II: DPs from Europe and Russian refugees from China. To that end, data contained in the database on DPs in the State of São Paulo, consolidated by Salles et al. (2013), was systematized and analyzed. Research revealed that the Brazilian policy on admission of DPs as industrial workforce had direct impact on the profile of the Russian population selected to immigrate to Brazil, mainly moving to the capital of the State of São Paulo. Russian refugees from China had a different demographic and social profile; the group had the most women and children and employed predominantly in the service sector. The professional characteristics of these two groups determined their distribution in the districts of São Paulo. As Europe's Russian DPs moved to peripheral and industrial districts, Russians from China settled in neighborhoods closer to the city center.

El presente artículo tiene como objetivo investigar las principales características de dos grupos de rusos llegados al estado de San Pablo tras la Segunda Guerra Mundial: los desplazados de la guerra provenientes de los campamentos para desplazados de Europa y los refugiados rusos procedentes de China. Para ello sistematizaron y analizaron los datos contenidos en el banco de datos sobre los desplazados de guerra en San Pablo, consolidado por Salles et al. (2013). La investigación reveló que la política brasileña de admisión a los desplazados de guerra como mano de obra industrial tuvo un impacto directo en el perfil de la población rusa seleccionada para inmigrar al país, la cual se dirigió predominantemente a la capital paulista. Los refugiados rusos llegados de China presentaron un perfil demográfico y social distinto, con evidencias de una mayor proporción de mujeres y niños y empleada en el sector de servicios. Las características profesionales de los dos grupos determinaron su distribución por los barrios de San Pablo. Mientras los desplazados de guerra de Europa se dirigieron a los barrios periféricos e industriales, los rusos provenientes de China se instalaron en los barrios más cercanos al centro de la ciudad.

Genetic Polymorphisms of Cytochrome P450 Enzymes and Transport Proteins in a Russian Population and Three Ethnic Groups of Dagestan.

AIM: The objective of this study was to investigate the prevalence of polymorphic markers of the CYP2C19, CYP2C9, CYP2D6, SLCO1B1, and ABCB1 genes among the three ethnic groups in Dagestan and compare it with the carrier frequency of these markers among the Russian population living in Moscow. METHODS: The study involved 186 healthy, unrelated, and chronic medication-free volunteers (53 males and 133 females) of the three ethnic groups in the Dagestan Republic: 46 Laks, 90 Avars, and 50 Dargins. Genotyping was performed using real-time polymerase chain reaction-based methods. The allelic prevalences of the three Dagestan peoples were compared with ethnic Russians from the Moscow region. RESULTS: Statistically significant differences for the following gene polymorphisms: CYP2C19*17, CYP2C9*3, ABCB1 (C3435T), SLCO1B1*5 were found between the Russian population and the three ethnic groups of the Dagestan republic. CONCLUSION: The data obtained from this study will help with prioritization genotyping in the region.

The Relationship between Body Mass Index and 10-Year Trajectories of Physical Functioning in Middle-Aged and Older Russians: Prospective Results of the Russian HAPIEE Study.

OBJECTIVE: To investigate the associations of overweight and obesity with longitudinal decline in physical functioning (PF) among middle-aged and older Russians. DESIGN: Prospective cohort study. SETTING: Four rounds of data collection in the Russian Health, Alcohol and Psychosocial factors In Eastern Europe study with up to 10 years of follow-up. PARTICIPANTS: 9,222 men and women aged 45-69 years randomly selected from the population of two districts of Novosibirsk, Russia. MEASUREMENTS: PF score (range 0-100) was measured by the Physical Functioning Subscale (PF-10) of the 36-item Short Form Health Survey (SF-36) at baseline and three subsequent occasions. Body mass index (BMI), derived from objectively measured body height and weight at baseline, was classified into normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obesity class I (BMI 30.0-34.9), and obesity class II+ (BMI≥35.0). RESULTS: The mean annual decline in the PF score during the follow-up was -1.92 (95% confidence interval -2.17; -1.68) in men and -1.91 (-2.13; -1.68) in women. At baseline, compared with normal weight, obesity classes I and II+ (but not overweight) were associated with significantly lower PF in both sexes. In prospective analyses, the decline in PF was faster in overweight men (difference from normal weight subjects -0.38 [-0.63; -0.14]), class I obese men and women (-0.49 [-0.82; -0.17] and -0.44 [-0.73; -0.15] respectively) and class II+ obese men and women (-1.13 [-1.73; -0.53] and -0.43 [-0.77; -0.09] respectively). Adjustment for physical activity and other covariates did not materially change the results. CONCLUSIONS: PF decreased more rapidly in obese men and women than among those with normal weight. The adverse effect of high BMI on PF trajectories appeared to be more pronounced in men than in women, making more extremely obese Russian men an important target population to prevent/slow down the process of decline in PF.

Efficient dynamic programming algorithm with prior knowledge for protein ß-strand alignment.

One of the main tasks towards the prediction of protein ß-sheet structure is to predict the native alignment of ß-strands. The alignment of two ß-strands defines similar regions that may reflect functional, structural, or evolutionary relationships between them. Therefore, any improvement in ß-strands alignment not only reduces the computational search space but also improves ß-sheet structure prediction accuracy. To define the alignment scores, previous studies utilized predicted residue-residue contacts (contact maps). However, there are two serious problems using them. First, the precision of contact map prediction techniques, especially for long-range contacts (i.e., ß-residues), is still not satisfactory. Second, the residue-residue contact predictors usually utilize general properties of amino acids and disregard the structural features of ß-residues. In this paper, we consider ß-structure information, which is estimated from protein ß-sheet data sets, as alignment scores. However, the predicted contact maps are used as a prior knowledge about residues. They are used for strengthening or weakening the alignment scores in our algorithm. Thus, we can utilize both ß-residues and ß-structure information in alignment of ß-strands. The structure of dynamic programming of the alignment algorithm is changed in order to work with our prior knowledge. Moreover, the Four Russians method is applied to the proposed alignment algorithm in order to reduce the time complexity of the problem. For evaluating the proposed method, we applied it to the state-of-the-art ß-sheet structure prediction methods. The experimental results on the BetaSheet916 data set showed significant improvements in the execution time, the accuracy of ß-strands' alignment and consequently ß-sheet structure prediction accuracy. The results are available at http://conceptsgate.com/BetaSheet.

Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in Russians: Replication Study.

In search of genetic markers of myocardial infarction (MI) risk, which have prognostic significance for Russians, we performed a replication study of MI association with genetic variants of PCSK9 (rs562556), APOE (epsilon polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS (rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198 controls. Significant MI association was observed with variants of the lipid metabolism genes (PCSK9, APOE and LPL), and of eNOS. The SNPs in the MTHFR gene and the 9p21 region were not significantly associated with MI one by one but were included in several different MI-associated allelic combinations identified by multilocus analysis. Since we have not revealed nonlinear epistatic interactions between the components of the identified combinations, we postulate that the cumulative effect of genes that form a combination arises from the summation of their small independent contributions. The prognostic significance of the additive composite model built from the PCSK9, APOE, LPL, and eNOS genes as genetic markers was assessed using ROC analysis. After we included these markers in the previously published composite model of individual genetic risk of MI, the prognostic efficacy in our sample reached AUC = 0.676. However, the results obtained in this study certainly need to be replicated in an independent sample of Russians.

Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic Russian individuals from Moscow, Russia.

Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms. Genotype data are available in the Allele Frequencies Net Database under identifier AFND 3367 and the population name "Russia Moscow Cytokine".

Possible approaches to CYP2C9-guided prescription of sulfonylureas in Russia.

AIM: To evaluate a possible role of CYP2C9 genotyping for sulfonylureas (SUs) prescription in Russia. MATERIALS & METHODS: We have collected the current data on correlation between SUs pharmacodynamics and CYP2C9 polymorphisms. We have evaluated the frequency of CYP2C9 polymorphisms in Russia by reviewing the literature published from 2004 to 2015 on Russian CYP2C9. RESULTS: The genotype *1/*1, which confers risk for treatment failure, has a higher frequency (81.92%) in the non-Caucasians than that (64.92%) in the Caucasians. The Caucasians have a frequency (3.58%) of the poor metabolizers (*2/*2, *2/*3 and *3/*3) eight-times higher than that (0.44%) in the non-Caucasians, predisposing an increased risk of hypoglycemia. CONCLUSION: Considering the received data and the existed knowledge on CYP2C9 influence on SUs pharmacokinetics and pharmacodynamics, we propose a possible approach to CYP2C9-guided SUs prescription for Russians.