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Data on the frequencies of all (50412) surnames in a total population of 849399 people have been treated by various methods of multivariate statistics (cluster analysis, multidimensional scaling, and factor analysis) to show that 22 district populations of the Central Chernozem region of Russia form a definite, ordered system of population groups. All raions (administrative districts) of Belgorod oblast (administrative region) have been grouped into four clusters corresponding to the actual geographic locations of the populations. Districts of the eastern cluster are characterized by very specific spectrum and frequencies of surnames; districts of the western cluster differ in a high proportion of Ukrainian surnames [ABSTRACT FROM AUTHOR]

Changes in the endogamy indices of district populations of the Central Chernozem region of Russia during the past 100 years were studied. The size of an elementary population in this region increased from that of a rural municipality in the mid-20th century to that of an administrative district in the late 20th century. [ABSTRACT FROM AUTHOR]

The characteristics of the gene pools of indigenous populations of Ukraine and Belarus have been studied using 28 alleles of 10 loci of biochemical gene markers (HP, GC, TF, PI, C′3, ACP1, GLO1, PGM1, ESD, and 6-PGD). The gene pools of the Russian and Ukrainian indigenous populations of Belgorod oblast (Russia) and the indigenous populations of Ukraine and Belarus have been compared. Cluster analysis, multidimensional scaling, and factor analysis of the obtained data have been used to determine the position of the Belgorod population gene pool in the Eastern Slavic gene pool system. [ABSTRACT FROM AUTHOR]

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low (0.00003 < < f*r < 0.00022, $$\overline {f_r^ * } $$ = 0.00015) and moderate (0.00023 < f*r < 0.00042, $$\overline {f_r^ * } $$ = 0.00029) inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*r < 0.00125, $$\overline {f_r^ * } $$ = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision. [ABSTRACT FROM AUTHOR]

In this work, the associations of polymorphism of candidate genes of arterial hypertension with the development of severe preeclampsia (PE) in the population of the Central Chernozem region of Russia were studied. Genotyping of five polymorphic variants (rs1799945 of the HFE gene, rs8068318 of the TBX2 gene, rs1173771 of the AC025459.1 gene, rs932764 of the PLCE1 gene, rs167479 of the RGL3 gene) was performed in 217 women with severe PE and 235 pregnant women with moderate PE. It was revealed that the G allele and the GG genotype of the rs167479 polymorphic locus of the RGL3 gene were associated with the risk of severe PE according to allelic (OR = 1.35, рperm = 0.02), additive (OR = 1.36, рperm = 0.02), and recessive (OR = 1.61, рperm = 0.04) genetic models. It has been established that this polymorphic locus is localized in a functionally active region of the genome that performs the functions of enhancers and promoters in various organs and tissues, is an area of hypersensitivity to DNase-1 and a binding site with nine transcription regulatory factors, and is associated with the expression level of the CTC-510F12.3 gene in the pituitary gland. In addition, rs167479 identifies a missense mutation that leads to the substitution of the amino acid Pro162His in the RalGDS-like3 protein and has a predictor potential of "PROBABLY DAMAGING." [ABSTRACT FROM AUTHOR]

A replicative study of associations of the LOXL1 gene polymorphism with primary open-angle glaucoma (POAG) in the female population of the Central Chernozem region of Russia was performed. The work was done in the design "patients–control." The study sample consisted of 290 women with POAG and 220 women in the control group. Three polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, rs893818) were genotyped by PCR (Tag-Man probe technology). The study revealed that SNPs of the LOXL1 gene (rs2165241, rs4886776, rs893818) are associated with POAG in women of the Central Chernozem region of Russia: allele C of rs2165241 (OR = 0.33–0.45 at pperm ≤ 0.0005), alleles A of rs4886776 (OR = 0.62–0.63 at pperm ≤ 0.031) and rs893818 (OR = 0.53–0.62 at pperm ≤ 0.007), and the CAA haplotype of rs2165241–rs4886776–rs893818 (OR = 0.56 at pperm = 0.022) are protective for the development of the disease, and the TGG haplotype (OR = 2.19 at pperm = 0.001) is associated with an increased risk of developing POAG in women. [ABSTRACT FROM AUTHOR]

Gender-specific features of associations of functionally significant polymorphic loci of matrix metalloproteinase genes with the development of peptic ulcer disease (PUD) in the population of the European part of Russia were studied. The study included 305 men (patients with PUD—188, control group—117) and 441 women (patients with PUD—211, control group—230). Ten functionally significant polymorphic loci of matrix metalloproteinase genes were genotyped: rs1799750 MMP1, rs243865 MMP2, rs679620 MMP3, rs1940475 MMP8, rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 of the MMP9 gene. Associations of polymorphic loci of MMP genes with PUD were studied by logistic regression (dominant, recessive, and additive genetic models of allele interaction were evaluated). It was found that alleles C rs3918249 (OR = 1.61, pperm = 0.048) and G rs17576 (OR = 1.48–2.08, pperm ≤ 0.042) of the MMP9 gene were risk factors for the occurrence of PUD in men. In women, the 2G rs1799750 allele of the MMP1 gene had a protective value for the development of the disease (OR = 0.74, pperm = 0.047). Polymorphic loci associated with PUD in men and women exhibit pronounced epigenetic effects (they affect the affinity of DNA motifs for various transcription factors, are located in the region of promoters and enhancers in the stomach and duodenum, and are associated with gene expression in various parts of the digestive system). Gender-specific features of associations of polymorphism of MMP genes with the development of PUD were revealed: rs3918249 and rs17576 of the MMP9 gene determine the susceptibility to the development of PUD in men, and rs1799750 of the MMP1 gene determines the susceptibility in women. [ABSTRACT FROM AUTHOR]

Polymorphic variants of matrix metalloproteinase (MMP) genes were tested for association with breast cancer (BC) in women of the Central Black Earth Region (CBER) of Russia with consideration to whether a patient has or does not have a family history of BC. The study included 358 BC patients (of which 68 had a family history of BC) and 746 control women. Genotyping was performed at ten polymorphic MMP loci: rs1799750 of MMP1; rs243865 of MMP2; rs679620 of MMP3; rs1940475 of MMP8; and rs17576, rs17577, rs3918242, rs2250889, rs3787268, and rs3918249 of MMP9. Logistic regression was performed to assess the associations of the MMP variants with BC in the patient subgroups with or without a family history of BC (the control group was the same for the two subgroups). Low risk of BC in women with a family history of BC was associated with MMP2 rs243865 (OR 0.53–0.54, pperm ≤ 0.03) and MMP9 rs2250889 (OR 0.36–0.37, pperm ≤ 0.04). Higher risk of BC in women without a family history of BC was associated with MMP9 rs3787268 (OR = 2.16, pperm = 0.03) and the following haplotypes at the MMP9 polymorphisms (pperm ≤ 0.05): CA at rs3918249–rs17576 (OR = 2.15), ССА at rs3918242–rs3918249–rs17576 (OR = 1.69), ССAG at rs3918242–rs3918249–rs17576–rs3787268 (OR = 1.69), and CAGCG at rs3918249–rs17576–rs3787268–rs2250889–rs17577 (OR = 3.06). Three haplotypes were associated with a low risk of BC in women without a family history of BC: GG at rs17576–rs3787268 (OR = 0.60), GGC at rs17576–rs3787268–rs2250889 (OR = 0.63), and CGG at rs3918249–rs17576–rs3787268 (OR = 0.62). [ABSTRACT FROM AUTHOR]

The associations of genes differentially expressed in the placenta with the risk of preeclampsia in women in Central Russia were studied. The study was conducted on a sample of 366 pregnant women with preeclampsia and 631 women in the control group. All pregnant women underwent typing of nine specially selected SNPs of genes differentially expressed in the placenta. Associations of SNPs of candidate genes with preeclampsia were assessed using logistic regression. For polymorphisms that showed associations with PE, their functional effects were assessed in silico. It was established that the G allele rs36011588 TMEM136 was a protective factor (OR = 0.65), and the CA haplotype of the rs2532058–rs66707428 PPP1R12C was a risk factor (OR = 1.21) for the development of preeclampsia. The associations of these SNPs with developing preeclampsia may be due to their important epigenetic significance: they are located at the sites of modified histones in the regions of promoters and enhancers, in DNase-hypersensitive sites, in binding sites for regulatory proteins, and in the binding domains for transcription factors. Also, these loci are associated with the level of transcription and alternative splicing in tissues pathogenetically significant for the development of preeclampsia. [ABSTRACT FROM AUTHOR]

Inconsistent results of association studies investigated the role of glutathione S-transferase genes in idiopathic male infertility may be explained by ethnical differences in gene-gene and gene-environment interactions. In this study, we investigated a joint contribution of GSTM1, GSTT1 and GSTP1 gene polymorphisms and cigarette smoking to the risk of idiopathic infertility in Russian men. DNA samples from 203 infertile and 227 fertile men were genotyped by a multiplex polymerase chain reaction ( GSTM1 and GSTT1 deletions) and PCR-restriction fragment length polymorphism ( GSTP1 I105V) methods. The GSTP1 genotype 105 IV was associated with increased risk of male infertility ( OR = 1.50 95% CI 1.02-2.20 P = 0.04). Genotype combinations GSTP1 105 II/ GSTT1 del (G1), GSTM1 del/ GSTT1 del (G2) and GSTM1 + / GSTT1 del (G3) were associated with decreased risk of male infertility ( P ≤ 0.003), whereas a genotype combination GSTP1 105 IV/ GSTT1 + (G4) was associated with increased disease risk ( P = 0.001). The genotype combinations G3 and G4 showed a significant association with infertility in smokers; however, nonsmokers carriers did show the disease risk. In conclusion, GSTM1, GSTT1 and GSTP1 genes are collectively involved in the development of idiopathic male infertility and their phenotypic effects on the disease risk are potentiated by cigarette smoking. [ABSTRACT FROM AUTHOR]

The associations of single nucleotide polymorphisms of the LHCGR gene with the formation of endometrial hyperplasia in the Russian population were studied. Genotyping of four loci of the LHCGR gene (rs4953616, rs4374421, rs6729809, rs7579411) was performed in 520 patients with endometrial hyperplasia (EH) and 981 women of the control group. A significant contribution to the susceptibility to endometrial hyperplasia of the rs7579411 polymorphism of the LHCGR gene has been established. The genotype C/C rs7579411 of the LHCGR gene is risky for EH (OR = 1.26, p = 0.05), whereas the allelic variant T rs7579411 of the LHCGR gene is a protective factor for EH (OR = 0.79, pperm = 0.05). The rs7579411 locus of the LHCGR gene has significant epigenetic effects (located in DNA regions marking regulatory sequences (enhancers)) and is associated with the expression of the STON1-GTF2A1L gene in organs and tissues (thyroid gland, peripheral blood) involved in the pathophysiology of the disease. At the same time, the allele T rs7579411 of the LHCGR gene is associated with low transcriptional activity of the STON1-GTF2A1L gene (β = –0.25). [ABSTRACT FROM AUTHOR]

The mean distance between birthplaces of spouses (σ, σ′), the proportion of medium migrations ( k), and the effective migration pressure ( Me) have considerably increased, and the linear systematic pressure coefficient ( b) has decreased in the human population of the Central Chernozem region during the past 50 years. However, the local inbreeding level ( a), which is determined by both an increase in the migration intensity and a decrease in the effective population size ( Ne), has remained practically unchanged. A change in the regional administrative structure has affected the genetic structure of populations. In the 1950s, raions (administrative districts) of Kursk and Voronezh oblasts (regions) were similar with respect differentiation parameters, whereas the oblasts considerably differed from each other. At present, some Malecot’s isolation-by-distance parameters for the populations of the districts that were included to Belgorod oblast in 1954 are lower and similar to those for the districts that remain in Kursk and Voronezh oblasts. [ABSTRACT FROM AUTHOR]

The frequencies of 33 alleles of 12 loci of immunological and biochemical gene markers (AB0, RH, HP, GC, TF, PI, C′3, ACP1, GLO1, PGM1, ESD, and 6-PGD) have been estimated in the indigenous Russian and Ukrainian populations of Belgorod oblast. Differences of the Belgorod population from other populations of Russia with respect to the genetic structure have been determined. It has been found that the frequency distributions of all alleles studied in the Belgorod population are similar to those typical of the genetic structure of Caucasoid populations. [ABSTRACT FROM AUTHOR]

The gene pool of the entire population of all the 21 raions (districts) of the Belgorod oblast (region) has been studied using anthroponymic data. Considerable geographic variations of the number of surnames and the degree of population subdivision (0.00003 < f < 0.00125) in the 21 districts have been demonstrated. Districts with low population subdivision levels are mainly located in the central and southwestern raions of the Belgorod oblast, contain an urbanized area (city), and border on Ukraine (they are characterized by a considerable Ukrainian immigration). Urbanization significantly affects the population structure of the Belgorod oblast. In urbanized districts, rural populations lack the relationships between the population size, number of surnames, and population subdivision level ( f r). [ABSTRACT FROM AUTHOR]

We studied the associations of newborn weight with polymorphic loci of growth factor genes in pregnant women with preeclampsia (PE) and considered their regulatory potential. In the group of pregnant women with PE (n = 190), a molecular genetic study of five polymorphic loci of growth factor genes was performed: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFβ1. Newborn somatometry was performed using standard methods. Associations of the studied polymorphic loci with newborn weight were studied using log-linear regression analysis. It was found that the genetic risk factor for the birth of small children in pregnant women with PE is the allele C of the rs833061 polymorphism of the VEGFA gene (pperm = 0.002): women with the T/T genotype have the highest newborn weight (on average 3524 g), while women with the C/C genotype have the minimum newborn weight (on average 3415 g). It is shown that the allele C of polymorphic locus rs833061 is associated with low transcription of the VEGFA gene in the thyroid gland and a higher level of alternative splicing of the VEGFA gene transcript in skeletal muscle, increases the affinity of DNA for transcription factors BCL, Pax-5, and Znf143, and affects the interaction of DNA with more than 20 different regulatory proteins (CTCF, RAD21, ZNF263, MAX, etc.). It is revealed that polymorphism rs833061of the VEGF gene in pregnant women with PE is associated with weight of the newborn and has considerable regulatory potential. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine associations of single nucleotide polymorphisms, rs1045642 within the MDR1 gene and rs1799930 within the NAT2 gene, with the risk of colorectal cancer (CRC) in the population of Central Russia. DNA specimens were obtained from 178 patients with CRC (87 males and 91 females) and 327 age-matched healthy controls (179 males and 148 females). Genotyping was performed using real-time PCR. Association of the studied SNPs with the risk of CRC was evaluated using logistic regression analysis. It was demonstrated that MDR1 rs1045642 polymorphism was associated with the increased risk of CRC after correction for gender, age, and smoking (OR = 1.41, 95% CI = 1.09–1.83; P = 0.008). A gender-stratified analysis showed that MDR1 rs1045642 was associated with the increased risk of CRC only in females (OR = 1.62, 95% CI = 1.11–2.35; P = 0.01). In males, no association between MDR1 rs1045642 and CRC was found. Association between MDR1 rs1045642 and the increased risk of colorectal cancer in Russian females from Central Russia was revealed. [ABSTRACT FROM AUTHOR]

Endometriosis is a process when benign growth of tissue is found outside of the uterus, the morphological and functional properties of such are alike endometrial [1-4]. The purpose of the study is an analysis of the role of a combination of four genes rs1514175, rs2241423, rs13111134 and rs5930973 in the formation of endometriosis among the population of the Central Chernozem Region of Russia. Material and methods: 1376 individuals were involved in the study group: 395 patients with endometriosis and 981 female control group. Women of Russian nationality who are native of the Central Chernozem Region of the Russian Federation and who aren't relatives were included in the samples of patients and controls. Venous blood was material for the study in a volume of 6 ml taken from the median cubital vein of the proband. The allocation of genomic DNA from peripheral blood was carried out by phenol-chloroform extraction. Study of the polymorphism was carried out using the method of polymerase chain reaction using appropriate primers and probes on the thermocycler IQ5. Results: genotyping of the four studied molecular-genetic markers was conducted. Studying of the distribution of genotypes at the studied loci among the patients with endometriosis and in the control group revealed that Hardy-Weinberg equilibrium (p>0.05) is performed for them. It was found that among patients with endometriosis was the lowest frequency of combinations of genetic variants with rs1514175 with A rs2241423 with A rs13111134 and G rs5930973 (of 8.55%) compared to the control group (13,54%, p=0.006; OR=0,60, 95% CI: 0,40-0,89). Conclusions. In the study it was found that the combination of genetic markers with rs1514175 with A rs2241423 with A rs13111134 and G rs5930973 (OR=0,60) reduces the risk of developing endometriosis among women of the Central Chernozem Region of Russia. [ABSTRACT FROM AUTHOR]

Preeclampsia is a multisystem pathological condition that occurs in the second half of pregnancy (after 20 weeks), characterized by arterial hypertension in combination with proteinuria (=3 g/l, in daily urine), often with edema and signs of organ/multisystem dysfunction. Preeclampsia (PE) is a serious complication of pregnancy, resulting in the onset of premature labor, detachment of normally situated placenta. The purpose of this study was to examine the Association of gene polymorphisms of the renin-angiotensin-aldosterone system with the functional status of the fetus of pregnant women with preeclampsia [1-4]. The study group included 132 pregnant women with preeclampsia. The average age of women surveyed was 27.98±5.29 years. To assess the functional state of the fetus is determined by uterine-fetal-placental blood flow (index of resistance (IR) left and right uterine artery and umbilical artery) and basal heart rate of the fetus. All pregnant women carried out the typing of genetic polymorphisms of the reninangiotensin- aldosterone system: angiotenzinoguena (-6A/G AGT) and angiotensin-converting enzyme (I/D ACE). For the description of indicators were used the median (Me) and interval scale (Q25-Q75), Mann-Whitney test. As a result of the study revealed that pregnant women with genotype-6 AGT, have lower basal heart rate of the fetus (median 137.0 BPM, interquartile range 130.0-146.0 BPM), in comparison with women with the genotype -6AG and -6GG AGT (median 143.0 beats/min, lower quartile - 136.0 beats/min, upper quartile - 152.0 beats/min, p=0.02). Reliable associations of polymorphism I/D ACE with the functional status of the fetus were not detected (p>0.05). Thus, when examining the associations consider genetic polymorphisms of the renin-angiotensin-aldosterone system with the functional status of the fetus the connection of genotype-6?? AGT with lower basal heart rate of the fetus had been established. [ABSTRACT FROM AUTHOR]

We conducted the first genetic analysis of a wide a range of rural Russian populations in European Russia with a panel of DNA markers commonly used in Human DNA identification. We examined a total of 647 samples from indigenous ethnic Russian populations in Arkhangelsk, Belgorod, Voronezh, Kursk, Rostov, Ryazan, and Orel regions. We employed a multiplex genotyping kit, COrDIS Plus, to genotype Short Tandem Repeat (STR) loci, which included markers officially recommended for DNA identification in the Russian Federation, the United States, and the European Union. In the course of our study, we created a database of allele frequencies, examined the distribution of alleles and genotypes in seven rural Russian populations, and analyzed the genetic relationships between these populations. We found that, although multidimensional analysis indicated a difference between the Northern Russian gene pool and the rest of the Russian European populations, a pairwise comparison using 19 STR markers among all populations did not reveal significant differences. This is in concordance with previous studies, which examined up to 12 STR markers in urban Russian populations. Therefore, the database of allele frequencies created in this study can be applied for forensic examinations and DNA identification among the ethnic Russian population over European Russia. We also noted a decrease in the levels of heterozygosity in the northern Russian population compared to southern and central Russian populations, which is consistent with trends identified previously using classical gene markers and analysis of mitochondrial DNA. [ABSTRACT FROM AUTHOR]

Yu.P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool. [ABSTRACT FROM AUTHOR]