[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.

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.

[Analysis of the genetic and demographic structure of populations from Aginskii Buryat district contrasting in habitation conditions].

Genetic and demographic characteristics of populations from two settlements from the Aginskii Buryat district of Trans-Baikal krai (Alkhanai and Orlovskii) were studied. It was demonstrated that the mononational Buryat settlement of Alkhanai, located in the agrarian Dul'durginskii region of the district far from large settlements and transport highways, is characterized by a large prereproductive volume (45%) and by a small share of individuals from the elderly age group (16.4%). A shift in age characteristics in the Buryat group (36.6 and 22.4%, respectively) was detected in the urban settlement of Orlovskii with a population of mixed ethnic composition, located in a densely populated industrialized part of the district. A modified sex ratio was also demonstrated in Alkhanai as opposed to the Buryat part of the Orlovskii population (sex indices were 0.94 and 0.99). Analysis of population mixture was conducted; marriage structure and migrations were described. The endogamy index of the Alkhanai locality was 0.41; in the group of Buryats from Orlovskii, 0.09. A decrease in the amount of pregnancies and births and a larger distribution of family planning practice among Buryats from Orlovskii were detected. The average amount of births of living children per woman in Alkhanai was 5.11; in Buryats from Orlovskii, 3.90. The selection pressure was estimated as low by means of the Crow index (I(tot) 0.28-0.48). In all described groups, a component that characterizes differential fertility (I(f)) exceeds the child mortality component (I(m)).

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.

[N-aсetyltransferase (NAT2) gene polymorphism and gene network analysis]. / Polimorfizm variantov gena N-atsetiltransferazy 2 (NAT2) i analiz gennoi seti.

To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.

[Genetic variability of hepatitis B virus isolates among population of Shuryskarsky area of Yamal-Nenets autonomous region].

UNLABELLED: The purpose of this work was to determine occurrence of serological markers of hepatites B and to describe subtypes of a superficial antigen and genotypes of hepatitis B virus (HBV) isolates among indigenous population of Yamal-Nenets Autonomous Region (YNAR), Russia. METHODS: We investigated 657 serum samples from inhabitants of Shuryskarsky area of YNAR. ELISA method was used to define the hepatitis B markers: HBsAg, anti-HBs (total) and anti-HBc (IgG and IgM). The HBsAg-positive samples were PCR-tested for the presence of HBV DNA. Genotyping of isolates was by sequencing of the Pre-Sl/Pre-82/S region of HBV genome and phylogenetic analysis. Definition of HBsAg subtypes was executed by two methods: ELISA with subtype-specific monoclonal antibodies and S-gene nucleotide sequence analysis. RESULTS: The following occurrence of hepatitis B markers was observed: HBsAg - 3.2%, anti-HBs (total) - 36.2%, anti-HBc IgG - 30.3%, anti-HBc IgM - 1.6%. Frequency of carrying even one of the markers in the observed population was 47.5%. HBV DNA was found in 17 HBsAg-positive samples. Pre-SI, Pre-S2 and S regions sequences were determined for all HBV DNA-positive samples. The phylogenetic analysis showed an accessory of all investigated HBV isolates to genotype D. HBsAg subtypes distribution appeared the following: ayw2 - 23.5%, ayw3 - 70.6%, adw2 - 5.9%. Results of definition of the subtype ELISA method and by the analysis of S gene nucleotide sequences have coincided in 10/11 (90.1%) cases. CONCLUSIONS: The indigenous population of Shuryskarsky area of YNAR belongs to groups with average HBV carrying. Absolute domination of genotype D (subtypes ayw2, ayw3 and adw2) was revealed. High percentage of concurrence of HBsAg subtypes detected by the ELISA method and method of the analysis of S gene primary structure (90%) was observed. Sequencing of HBV S-gene is preferable to define HBsAg subtypes.

[The effect of marriage migration on the genetic structure of the Taimyr Nganasan population: genealogical analysis inferred from MtDNA markers].

The marriage structure of Nganasans during the time period from 1796 to 1991 and genealogy of carriers of mitochondrial DNA haplotypes was studied in a sample of 280 individuals. It was shown that, from the beginning of its formation to the late 1970s, the population exhibited high endogamy (1976, 83.8%; 1926, 88.4%; 1976, 74.3%). The main source of traditional marriage migration (preferentially female) was populations of Entsy and, indirectly, Nentsy. Intense assimilation of Nganasans by the immigrant population, and to a lesser extent, by Dolgans, in the second half of the 20th century resulted in a reduction of endogamy index in Avam Nganasans to 42.5% by 1991. Assimilation by the immigrants was predominantly paternal, promoting preservation of the historically formed genetic diversity of the Nganasan mitochondrial gene pool. Genealogical analysis of mtDNA haplotypes showed that a relatively high total frequency of Western Eurasian mtDNA haplogroups (20.4%) in the Mongoloid (according to anthropological type) Nganasan population is explained not only by the common ethnic origin with Entsy and Nentsy, but also by direct marriage migration from the Entsy population and indirect marriage migration, from the Nentsy population. This migration led to accumulation of Entsy-Nentsy maternal lineages in the genealogy of Avam Nganasans (38.9% of the total number). Of all mtDNA haplotypes, 28.6% were introduced to Avam Nganasans by female Entsy and Nentsy, whereas the total frequency of these haplotypes was 0.204. Genetic diversity of mitochondrial DNA haplotypes was 0.935.

Relationships between left hemisphere predominance and disturbances of lipid metabolism in different ethnic groups.

The purpose of this study was to analyze the relationships between brain hemisphere predominance and disturbance of lipid metabolism in atherosclerosis in different ethnic groups. Three groups of subjects were examined: 52 healthy Selkups (the isolated ethnic population of the Far North), 50 healthy Russian men, living in Novosibirsk, and 78 Russian men, living in Novosibirsk, who had myocardial infarction before the age of 50. Blood cholesterol, low density lypoprotein (LDL) and high density lypoprotein (HDL) levels of the subjects with different brain functional asymmetry were compared. The lack of either hemisphere predominance is the most common among the Selkups. The population of Selkups as a whole showed low concentrations of cholesterol and LDL in comparison with both Russian groups. For all examined groups the pattern of lipid metabolism has been worsened for the subjects showing the left hemisphere predominance. The changes of lipid metabolism indices in subjects with the dominant left hemisphere is discussed.

Strong changes in lipoproteins and autoantibodies of blood serum of the Tundra Nency population as a result of environmental radiation on the territory they inhabit.

As a result of large-scale nuclear tests on the Novaya Zemlya test site (1955-62) the Tundra Nentsy population of Yamal-Nentsy autonomous region (YNAR) fell under the constant influence of incorporated radioactive isotopes (137Cs and 90Sr). Therefore, it is very important to analyze a possible spectrum of diseases of Tundra Nentsy population.

Genetic polymorphism of CYP1A1 and CYP2D6 in the Tundra Nentsi population of Siberia.

The purpose of this study was to establish the frequencies of CYP1A1 and CYP2D6 polymorphic genotypes in the Tundra Nentsi population, which is a small indigenous northern people living in Siberia and belonging to the Northern Mongoloid race. The frequencies of Ile/Ile, Ile/Val, and Val/Val genotypes in the Tundra Nentsi population, as determined by means of the allele-specific PCR, were 50.8%, 39.2%, and 10%, respectively. Thus, the Val allele frequency in Tundra Nentsi appeared to be as high (29.5%) as in the Japanese population (25%) reported elsewhere. Those frequencies in the reference group of Siberian Caucasians were in good agreement with the data reported elsewhere for other Caucasians, although the Val allele frequency observed in Siberia inhabitants (5.7%) was somewhat higher than those frequencies obtained for other Caucasian populations. By means of PCR followed by specific-site digestion with MvaI endonuclease, we analysed the frequencies of CYP2D6B allele in the Tundra Nentsi population. The frequencies of 2D6wt/2D6wt and 2D6wt/B in the group of 120 Nentsi were 84.2% and 15.8%, respectively, with no subject possessing the 2D6B/2D6B genotype. The group of Siberian Caucasians represented those frequencies as 67.7%, 27.1%, and 5.2%, respectively. In total, the frequency of CYP2D6B allele in the Tundra Nentsi population was half that in Caucasians (8.3% vs. 19%). Taken together, our data indicate that the frequencies of CYP2D6B and Val allele of CYP1A1 in Tundra Nentsi population are different from those obtained for Caucasians. We also found similarities in the CYP1A1 mutation frequencies in the Tundra Nentsi and Japanese populations.

Genetic polymorphisms of CYP1A1, GSTM1 and P53 genes in a unique Siberian population of Tundra Nentsi and its pharmacogenetic importance.

Complete data on the polymorphisms of CYP1A1, GSTM1 and p53 genes in Tundra Nentsi population, with known genealogical history are essential for the analysis of the "cancer susceptibility gene markers" distribution among different Oriental populations. The cytochrome P4501A subfamily is known to be responsible for the metabolic activation of aromatic compounds occurring in the products of gas mixture combustion, the main environmental pollutants in the north of western Siberia. Recently a close correlation was reported between development of some types of cancer and polymorphisms of human CYP1A1, GSTM1 and p53 genes. The frequency of the CYP1A1 Vol allele in the healthy part of the Tundra Nentsi population differs from those previously reported for Japanese and is more than 1.5 times higher. It is necessary to underline that homozygote Val genotype was present in 26% of non-healthy Tundra Nentsi, the incidence being 2.7-times higher in comparison with healthy population. GSTM1 gene deletion is present in 40% of Orientals and in 39% of Tundra Nentsi. Moreover, the share of individuals with null genotype among a group with chromosomal abnormalities and cancer was 63%, or 1.5 fold higher. Thus the prevalence of two polymorphic genes CYP1A1 and GSTM1 responsible for the biotransformation of polycyclic aromatic hydrocarbons was too high in the non-healthy group.

[Assessment of the status of biological health of the population of tundra Nentsy inhabiting northwestern Siberia from data on analysis of autoantibodies and lipoproteins from blood donors]. / Otsenka sostoianiia biologicheskogo zdorov'ia populiatsii tundrovykh nentsev Iamalo-Nenetskogo avtonomnogo okruga po dannym analiza autoantitel i lipoproteidov krovi donorov.

As a result of large-scale nuclear explosion on Novaya Zemlya test site (1955-62) the Tundra Nentsy population of Yamal-Nentsy autonomous region (YNAR) fell under constant influence of incorporated radioactive isotopes (137Cs and 90Sr). Therefore, it is very important to analyze a possible spectrum of diseases of Tundra Nentsy population. We have developed recently a new method for determination of concentrations of all main fraction and subfraction of lipoproteins (LP, 30 parameters) in human sera using small-angle X-ray scattering, and a general mathematical model to describe LP composition in human blood. The analysis of the 30 parameters characterizing fine spectrum of LPs in 374 YNAR natives showed that only approximately 10% of the donors are normal, while the indices for approximately 90% of the test subjects fall into the range of different pathologies (3-8% incidence in normal population, according to epidemiological studies). Moreover, we found that approximately 41% of European and approximately 56% of Tundra Nentsy have high level of autoantibodies to DNA and cardiolopine like the same for autoimmune diseases patients.

[Population structure of the forest Nentsi. IV. Immunoglobulin allotypes and the concentration and origin of Gm haplotypes with a null expression of the C gammal gene]. / Populiatsionnaia struktura lesnykh nentsev. Soobshchenie IV. Allotipy immunoglobulinov, kontsentratsiia i proiskhozhdenie Gm-gaplotipov s nulevoi ékspressiei C gammal-gena.

Serum blood samples from 796 of the total 1600 Forest Nentsi, the members of the isolate in the north-western part of Siberia were tested for the G1m (z, a, x, f), G2m (n), G3m (g, b0, b1, b3, b5, s, t) and Km (1) antigens. Significant heterogeneity in local Gm haplotype and Km1 allele frequencies has been found. The frequencies of "deleted" Gm (-; n; b) and Gm (-;..; g) haplotypes were found to be equal 0,020 and 0,004, respectively. When segregation disturbances for the Gm locus were inspected in 102 families, no apparent deviations from Mendelian expectations occurred. Blent, Oriental-Caucasian origin of Forest Nentsi has been confirmed by the presence of "Northern Oriental" Gm (za; b035st) and "Caucasian" Gm (f; b0135) markers showing the frequency of 0.199 and 136, respectively.

Distribution of hereditary variants of haptoglobin and transferrin in several human populations in Siberia. / Raspredlenie nasledstvennykh variantov gaptoglobina i transferrina v nekotorykh populiatsiiakh cheloveka v Sibiri

Haptoglobins and transferrins have been studied in nganasans from Taymir peninsula, in chelkantsi and kumandintsi from Altai and in 500 Russian inhabitants of Novosibirsk. Frequencies of Hp2 and TfB0-1 alleles in nganasams have been found to be the highest in the region. Transferrin polymorphism in the sample from Novosibirsk population seems to be maintained at the expense of four common alleles (C;B2;B0-1; DChi), in nganasans -- tow alleles (C and B0-1). No polymorphism has been observed in chelkantsi and kumandintsi. No rare transferrin variant has been found in the samples studied except homozygous B0-1 B0-1 in a child from nganasan family.

[Polymorphism of immunoglobulin Gm- and Km-allotypes in northern Altaians (western Sibiria)]. / Polimorfizm Gm- i Km-allotipov immunoglobilinov u severnykh altaitsev (Zapadnaia Sibir').

In two small adjacent groups-kumandinias and chelkanians-the distribution of G1m(a), G1m(x), G1m(f), G3m(b1), G3m(b5) and Km(1) serum allotypic markers was studied. Gmf;b haplotype frequency in kumandinians was found to be 0.310; in chelkanians living eastward it was 0.212. Gma and Gmax frequencies were observed to be 0.606 and 0.084 in the former and 0.687 and 0.101 in the latter. Km1 frequency was found to be 0.074 in kumandinians and 0.087 in chelkanians. Unusual Gm(a, f) henotype was observed in both groups with a frequency lesser than 5%.

[Heterozygosity and fertility in the Northern Selkup tribe]. / Geterozigotnost' i plodovitost' u severnykh sel'kupov.

The relationship between heterozygosity for 11 polymorphic loci and fertility of women having passed the menopause was studied in North-Siberian tribe North Selkup. Women with low level of heterozygosity were characterized by the highest values of variance of the number of livebirths and the index of early reproductive loss.

[Polymorphism of mitochondrial DNA in Northern Selkups]. / Polimorfizm mitokhondrial'noi DNK u Severnykh Sel'kupov.

The RFLPs detected by the AvaII, BamHI, EcoRV, KpnI, HaeIII, and RsaI restriction enzymes in the D-loop region of mitochondrial DNA of the Northern Selkups were analyzed. Frequencies of the rare variants were estimated for all polymorphic sites examined. A total of 16 mitotypes were described. Results were compared with the literature data on mitochondrial DNA polymorphism in Caucasoid and Mongoloid populations. High frequency of the KpnI bp 16129 site loss (28.14%) together with a remarkably reduced number of mitotypes in the group of variants with the frequency of 2% compared to the Russians and Mongols, was considered to be the most informative population feature of the Northern Selkups. All variants found in the Selkups, occurred more frequently in the Mongols than in Russians. Four out of ten rare variants (frequency < 2%) observed in the Selkups were detected in Mongols and Russians. The frequency of three of these variants was higher in the Russian population. Six mitotypes were characterized as Selkup-specific. These observations suggest a considerable reduction of mitochondrial gene pool diversity in Northern Selkups compared to larger ethnic groups of Mongoloids and Caucasoids. The structure of mitochondrial genome in Selkups is defined by the presence of the major Mongoloid and minor Caucasoid components, which suggests complex ethnogeny of the contemporary Selkup population.

[Genetic structure of an isolated native population group of northern Sibiria, the Nganasani (Tavgi) of the Taimyr. II. An analysis of intrapopulation variability]. / Geneticheskaia struktura obosoblennoi gruppy korennogo naseleniia Severnoi Sibiri--nganasan (tavgiitsev) Taimyra. Soobshchenie II. Analiz vnutripopuliatsionnoi izmenchivosti.

Chi-square contingency table analysis of phenotypic (genotypic) and gene frequencies of erythrocyte and blood serum groups and enzymes in a group of reindeer hunter and fishermen revealed heterogeneity within the population studied. Four out of twelve loci which have been compared were found to be involved in the process of differentiation into two local subgroups (subpopulations). No statistical differences have been observed between samples arbitrarily representing three generations. The data obtained support the hypothesis that the whole population still preserves the state of the stability. Traditional migration from adjacent populations close to nganasans by language and culture has made an important contribution into heterogeneity found in nganasans.

[Genetic and ecological study of aboriginal populations of northeastern Siberia. II. Polymorphic blood systems, immunoglobulin allotypes and other genetic markers in asian eskimos. Genetic structure of Bering sea eskimos]. / Geneticheskoe i ékologicheskoe izuchenie korennykh zhitelei severo-vostoka Sibiri. Soobshchenie II. Polimorfnye sistemy krovi, allotipy immunoglobulinov i drugie geneticheskie markery u aziatskikh éskimosov. Geneticheskaia struktura éskimosov Beringova moria.

Blood groups, immunoglobulin allotypes, serum proteins and red cell enzymes were tested in four populations of Asiatic Eskimos. 12 of 16 gene loci studied were found to be polymorphic. Analysis of covariance and variance matrices for gene frequencies of 8 Bering Sea populations revealed major aspects of regional genetic structure. Regression of average heterozygosity on genetic distance from centroid permitted us to interpret it in the light of counterbalancing action of systematic and non-systematic pressure. Analysis of R matrix containing gene frequencies for both Eskimo and Chukchi populations revealed two different clusters - more heterogeneous Eskimo cluster and less heterogeneous Chukchi cluster. Good fit was observed between regional genetic structure, history and geography.

[Population structure of the forest Nentsi. V. F-statistics, genetic distances and the average heterozygosity (compared to the Nganasani)]. / Populiatsionnaia struktura lesnykh nentsev. Soobshchenie V. F-statistika, geneticheskie distantsii i sredniaia geterozigotnost' (v sopostavlenii s nganasanami).

Aspects of population structure within two of the least disintegrated "anthropological isolates" in north-western (forest Nentsi) and north-central (Nganasani) Siberia were analysed on the basis of 14 polymorphic loci. The mean FIS values were found to be 0.008 in the forest Nentsi and -0.038 in the Nganasani. The negative FIS in the latter may be due to avoidance of close inbreeding. This is not the case with the Forest Nentsi who prefer matings of the uncle-niece and first cousin's type. The mean RST(FST) values of 0.026 for the forest Nentsi and 0.009 for less heterogeneous Nganasani fall within the range of values found in subdivided human groups with a similar pattern of material culture and economy. Analysis of covariance and variance matrices containing gene frequencies for seven forest Nentsi and three Nganasani subdivisions indicate that the population structure of both groups is the product of the counterbalancing action of genetic drift and migration. Pairwise genetic and geographic distance matrices between subpopulations within both groups are highly correlated, allowing us to ascribe more than 90 percent of variation among subdivisions of the Nganasani and almost 70 percent in the forest Nentsi to the effects of geographic barriers, namely distance. Mean locus heterozygosity was found to be higher in the forest Nentsi (0.332) than in the Nganasani (0.286) reflecting pronounced difference in their histories.