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The goal of this study was to investigate the association between the polymorphic loci of genes IL1B (rs16944), IL1RN (rs4251961), IL6 (rs1800795, rs1800796, rs1554606), IL8 (rs4073), IL10 (rs1800896), and TNFA (rs1800629) and breast cancer in women. The DNA samples of 521 women with breast cancer and 267 women without oncological pathology were studied. The study showed that age, concomitant chronic morbidity, and polymorphism of the IL6 gene are risk factors in postmenopausal women. Allele –572C (OR = 5.68; 95% CI = [2.70–11.97], pcor < 0.001), and haplotype rs1800796[C]–rs1800795[G]–rs1554606[G] (OR = 5.31, 95% CI = [1.87 – 15.10], pcor = 0.002) of the IL6 gene were associated with breast cancer. No association of loci in IL1B (rs16944), IL1RN (rs4251961), IL8 (rs4073), IL10 (rs1800896), or TNFA (rs1800629) was associated with the risk of breast cancer. The obtained data indicate that the –572C allele of the IL6 gene is associated with susceptibility in postmenopausal women to breast cancer. Our results can be useful for an understanding of the molecular mechanisms of breast cancer.

BackgroundN-acetyltransferase 2 plays a crucial role in the metabolism of a wide range of xenobiotics, including many drugs, carcinogens, and other chemicals in the human environment. The article presents for the first time data on the frequency of two important “slow” variants ofNAT2gene(NAT2*5, rs1801280 andNAT2*7, rs1799931),which significantly affect the rate of xenobiotics acetylation, among representatives of indigenous populations of Forest and Tundra Nenets in Northern Siberia. The aim of this study was to identify the frequencies of these variants and compare them with frequencies in other ethnic populations.ResultsNAT2*5(T341C) genotyping revealed frequencies of 28,0% and 38,6% for Tundra and Forest Nenets, respectively. The frequencies ofNAT2*7(G857A) variant were 9,8% and 8,2% for Tundra and Forest Nenets, respectively. Polymorphic variants frequencies for Nenets are intermediate between those in populations of Europeans and Asians. These results can probably be explained by the presence of both European and Asian components in Nenets gene pools.ConclusionsThe results of this study expand the knowledge ofNAT2polymorphism in world populations. These data may also help assess the genetic predisposition of Nenets to multifactorial diseases associated with polymorphism in theNAT2gene and, in general, contribute to the development of personalized medicine in reference to native people of Siberia.

Aim: To determine the differences in the frequencies of polymorphic variants at the rs4244285(*2), rs4986893 (*3), rs12248560 (*17), loci of the CYP2C19 gene, and the rs2305948 locus of the VEGFR-2...

Polymorphic variants of genes of enzymes of xenobiotic biotransformation (CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP2D6 (rs35742686), CYP2E1 (rs2031920), EPHX1 (rs1051740), GSTP1 (rs1138272, rs1695), GSTM1 (del), GSTT1 (del)), DNA reparation (XRCC1 (rs25489, rs25487, rs1799782), APEX1 (rs1130409), hOGG1 (rs1052133), PARP1 (rs1136410), XPD (rs13181), XPG (rs17655), XPC (rs2228001), ATM (rs1801516), NBS1 (rs1805794), XRCC2 (rs3218536), XRCC3 (rs861539), XRCC4 (rs2075685), Ligase IV (rs1805389)), antioxidant system (SOD2 (rs4880), GPx1 (rs1050450), CAT (rs1001179)), cell cycle control and apoptosis (TP53 (rs1042522)), cytokines (TGFβ (rs1800469), TNFα (rs1800629)), folate metabolism (MTHFR (rs1801133), MTR (rs1805087)), and chromosomal aberrations in blood lymphocytes of 288 miners of coal mines in Kuzbass, 365 workers of coal-fired thermal power plants, and 642 residents of Kemerovo oblast who did not work at industrial enterprises were analyzed. The frequency of chromosomal aberrations in the group of miners (4.06 ± 0.15%) and workers at thermal power plants (3.19 ± 0.09%) was significantly higher than in the group of individuals who did not work in production (1.53 ± 0.05%, p < 0.00001). The increased frequency of chromosome aberrations in miners is associated with genetic variants XPD rs13181 and XRCC4 rs2075685, and in power engineers with variants of the TGFβ gene rs1800469.

Aim. To study the influence of genetic factors on the risk of essential arterial hypertension (AH) and the course in patients of Russian and Buryat ethnicity.Material and methods. The study included 248 patients of the Russian and 92 patients of the Buryat ethnic group. All patients were evaluated for genotypes by ACE, ADRB1, ADRB2, ADRB3, CAT, NOS3, CYP11B2, AGT, STK39, EDN1, GNB3 markers. Following clinical data were determined: age, body mass index, smoking history, stage and degree of AH, the presence and nature of target organ damage, hereditary history. In the study, patients of the two ethnic groups were divided into the case and control groups depending on the presence or absence of AH.Results. In patients of the Russian ethnic group, an association of a more severe AH course with a burdened family history was revealed, in contrast to patients of Buryat nationality. In the Buryat group, the development of AH is associated with polymorphisms of the candidate genes ADRB3 (rs4994), GNB3 (rs5443), ACE (rs464994), STK39 (rs3754777), EDN1 (rs9349379). In the Russian group, ACE, EDN1, CYP11B2 (rs 1799998), GNB3, NOS3 (rs1799983), ADRB1 (rs1801253) genes had a significant contribution. When comparing the assortment of allele frequency of the ACE gene polymorphic marker among two ethnic groups, the “I” allele was found significantly more frequently in patients of Russian group.Conclusion. The results of the study revealed ethnic differences in the genetic features of essential AH. For the first time, an association between genetic markers encoding elements of the renin-angiotensin system, sympathoadrenal system, endothelial system and AH risk in patients of Buryat nationality was established. The identification of ethnic differences and genetic predisposition to AH, makes it possible to understand the role of the hereditary component of hypertension. We suppose that these data in conjunction with the influence of the environment, can help to develop one of the areas of personalized medicine.

The aim of this study was to assess which Mycoplasma pneumoniae genotypes were present in Moscow during the years 2015-2018 and whether the proportion between detected genotypes changed over time. We were also interested in the presence of macrolide resistance (MR)Mycoplasma pneumoniae. We performed multilocus variable-number tandem-repeat (VNTR) analysis (MLVA), SNP typing, and mutation typing in the 23S rRNA gene from 117 M. pneumoniae clinical isolates. Our analysis suggests two major MLVA types: 4572 and 3562. In 2017-2018, MLVA type 4572 gradually became predominant. In general, the SNP type range is the same as described earlier for European countries. The analysis of MR mutations showed that 7% of the isolates had an A2063G mutation in the 23S rRNA gene with no isolates carrying an A2064G mutation. In 2017-2018, MLVA type 4572 (SNP type 1) begins to spread in Moscow, which was widespread globally, especially in Asian countries. SNP typing of our sample showed higher discriminatory power than MLVA typing.

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.Poisk novykh misheneĭ dlia terapii dolzhen opirat'sia na rekonstruktsiiu gennoĭ seti zabolevaniia, opredelenie vzaimodeĭstviĭ genov, belkov i lekarstvennykh soedineniĭ. S pomoshch'iu onlaĭn-instrumentov bioinformatiki my proanalizirovali aktual'nyĭ na dannyĭ moment massiv dannykh, sviazannykh s metabolizmom ksenobiotikov, reguliruemykh genom N-atsetiltransferazy 2 (NAT2). Issledovanie allel'nogo polimorfizma gena NAT2 imeet prognosticheskoe znachenie, pozvoliaiushchee otsenivat' riski riada onkozabolevaniĭ i ikh povyshenie na fone kureniia i vozdeĭstviia khimicheskikh kantserogenov, v tom chisle lekarstvennykh preparatov. Tsel'iu dannogo issledovaniia iavilos' opredelenie u predstaviteleĭ korennogo nenetskogo naseleniia Severnoĭ Sibiri chastot dvukh vazhnykh “medlennykh” variantov gena NAT2 (NAT2*5, rs1801280 i NAT2*7, rs1799931), sushchestvenno vliiaiushchikh na skorost' atsetilirovaniia ksenobiotikov. Poluchennye chastoty polimorfnykh variantov u nentsev imeli promezhutochnye znacheniia mezhdu takovymi dlia evropeĭtsev i aziatov, chto, vozmozhno, obuslovleno osobennostiami ikh adaptatsii. My predlozhili model' raspredeleniia variantov gena NAT2, uchastvuiushchego v biotransformatsii ksenobiotikov, i vzaimodeĭstviĭ v sostave gennykh seteĭ dlia issledovaniia osobennosteĭ metabolizma u korennykh narodov Iamala.

Background. Breast cancer (BC) is the most common oncological disease in women in the world. The aim of study is to investigate the frequencies of mutations in BRCA1 5382insC (rs80357906), CHEK2 1100delC (rs555607708) and BLM c.1642 CT (rs200389141) genes and their relationship with the phenotypic features of BC in 104 young age women. Materials and methods. We studied 104 young age women with breast cancer. Typing of mutations BRCA1 5382insC, CHEK2 1100delC and BLM c.1642 CT genes were performed by real-time PCR followed by melting analysis. Results. The BRCA1 5382insC mutation was detected in 9.6% of BC patients. The BRCA1 5382insC mutation was correlated with the lack of expression of estrogen receptors (2 = 18.48, d(f) = 1, p 0.0001), the HER2/neo tumor receptor (2 = 5.61, d(f) = 1, p 0.02). The BRCA1 5382insC mutation was more often in the triple negative BC (2 = 17.42, d(f) = 3, p 0.001). Luminal A subtype of disease was observed the predominantly in non-carriers of the mutation BRCA1 5382insC (sporadic breast cancer). The founder mutations in the CHEK2 1100delC and BLM c.1642 CT genes were absent in young age women with BC. Conclusion. Our results confirm the high significance of detecting the BRCA1 rs80357906 mutation in young age women with BC for optimization of treatment tactic and for early diagnosis of BC.

Heredity plays an important role in the etiology of varicose veins (VVs). However, the genetic basis underlying this condition remains poorly understood. Our aim was to replicate top association signals from genome-wide association studies (GWASs) for VVs of lower extremities using 2 independent datasets-our sample of ethnic Russian individuals (709 cases and 278 controls) and a large cohort of British residents from UK Biobank (10 861 cases and 397 594 controls). Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562, rs7111987, rs6062618, and rs6905288 were validated in the UK Biobank individuals at a Bonferroni-corrected significance level. In Russian cohort, only rs11121615 reached a nominal significance level of P < .05. Results of original GWAS and replication studies were combined by a meta-analysis, and polymorphisms listed above as well as rs111434909 and rs4463578 passed a genome-wide significant threshold. Notably, the majority of these polymorphisms were located within or near genes involved in vascular development and remodeling, and regulation of inflammatory response. Our results confirm the role of these polymorphisms in genetic susceptibility to VVs and indicate the revealed genomic regions as good candidates for further fine-mapping studies and functional analysis. Moreover, our findings implicate inflammation and abnormal vascular architecture in VVs pathogenesis.

The study of the gene polymorphism of the system of biotransformation of xenobiotics is an important area of modern medical and genetic research. The aim of this work is to study the frequency of the alleles of the CYP1A1 (A2455G (*2C), rs1048943), CYP2D6 (A2549del (*3), rs35742686); G1846A (*4), rs3892097) genes of Teleuts (n = 115), Eastern Buryats (n = 132), Western Buryats (n = 280), their Métis (n = 56), and Russians of East Siberia (n = 122). Genotyping was performed using real-time PCR with competitive TaqMan allele-specific probes. The frequency of the CYP1A1*2C (2455G) allele was 28.8 % in the Eastern Buryat, 34.6 % in the Western Buryat, 16.7 % in the Teleut, and 31.3 % in the Métis cohort. The frequency of CYP1A1*2C (2455G) in the Russians of Eastern Siberia (4.1 %) corresponds to the frequency range found in European populations. A high-frequency occurrence of CYP1A1*2C (2455G) among Buryats and Teleuts may be indicative of a higher population-wide risk of diseases influenced by technogenic pollutants – substrates of CYP1A1. The CYP2D6*3 (2549del) allele was not detected in cohorts of indigenous populations, among Russians it was 0.4 %, and it was 2.7 % among Métis. The frequency of CYP2D6*4 (1846A) in Eastern and Western Buryats was 5.3 % and 4.3 %, respectively, for Teleuts it was 7.4 %. It was significantly higher in the Russian population (12 %), and among Métis (9.8 %). The obtained data makes it possible to predict a reduced risk of side effects of drugs and cancer associated with CYP2D6*3 (2549del) and CYP2D6*4 (1846A) in the Buryat and Teleut populations. However, metisation introduces new polymorphic variants into indigenous populations, shifts gene frequencies and changes the degree of risks.

Background Brain arteriovenous malformations (BAVMs) are formed by hypertrophied arterial vessels (afferents, feeders), a large number of arteriovenous shunts which become tangled to form a body (nidus) of malformation, which then expands draining proximal veins. The aim of this study was a replication of single nucleotide polymorphism (SNP) rs11672433 association with BAVM development with the subsequent meta-analysis of published data. Methods A total of 252 Russian patients with brain BAVMs and 480 control subjects were included in the present study. Genotyping was performed using real-time polymerase chain reaction with competitive hydrolysis probes. Results In our case–control study, we found no significant association with brain arteriovenous malformation for the SNP rs11672433 of ANGPTL4 gene (odds ratio .82, 95% confidence interval = .57-1.17 P value = .27) as well as in meta-analysis (odds ratio 1.18, 95% confidence interval = .81-1.73, P value = .39). Conclusions Our data showed that SNP rs11672433 was not associated with the BAVM Russian population and the following meta-analysis did not detect an association in total. Thus, in spite of the fact that ANGPTL4 (protein) participates in the angiogenesis regulation processes, we consider that SNP rs11672433, a high-frequency locus in the ANGPTL4 gene, does not influence the predisposition to BAVM or its effect is too small to be detected in the present size sample set.

Background. Squamous cell lung cancer (SCLC) is the most common form of lung cancer among men smokers. Mediators and products of inflammation can contribute to the initiation of carcinogenesis in smokers. The aim of study is to investigate the association between IL1B(rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), IL6 (rs1800795), IL10 (rs1800896) genes and SCLC depending on the duration of smoking in men. Materials and methods. We studied 324 patients with SCLC and 168 healthy men smokers. The typing of the IL1RN(rs2234663) gene polymorphism has analyzed by polymerase chain reaction (PCR). Detection of the IL1B (rs1143634) and IL6 (rs1800795) polymorphisms have performed by restriction fragment length analysis, as a restriction enzyme TaqI was used. The IL1B (rs16944), TNFA(rs1800629) and IL10 (rs1800896) genes polymorphisms have determined through TaqMan-real-time PCR. Results. The study showed, the age, duration of smoking and the number of cigarettes smoked per day were the main risk factors for SCLC in men (p 0.0001). The IL6 -174G allele was detected an additional risk factor of SCLC at a smoking duration of less than 35 years (OR = 1.68; 95 % CI: 1.12-2.51; pcor = 0,04). No association of IL1B (rs1143634, rs16944), IL1RN (rs2234663), TNFA (rs1800629), and IL10 (rs1800896) genes with the risk of SCLC in men was identified. Conclusion. The duration of smoking and rs1800795 IL6 gene polymorphism may influence on the susceptibility to SCLC in men. Our results can be useful in understanding the molecular mechanisms of development of SCLC.

The 23 polymorphic variants in genes encoding the enzymes of xenobiotics biotransformation (CYP1A1 (rs4646903), CYP1A2 (rs762551), GSTP1 (rs1138272, rs1695), GSTM1 (del), and GSTT1 (del)), DNA repair (XRCC1 (rs25489, rs25487), APEX1 (rs1130409), hOGG1 (rs1052133), ADPRT (rs1136410), XPD (rs13181), XPG (rs17655), XPC (rs2228001), ATM (rs1801516), NBS (rs1805794), XRCC2 (rs3218536), and XRCC3 (rs861539)), antioxidant system (MnSOD (rs4880) and GPx1 (rs1050450)), cell cycle control and apoptosis (TP53 (rs1042522)), DNA methylation (MTHFR (rs1801133) and MTR (rs1805087)), and chromosomal aberrations in lymphocytes in the workers at thermal power plants were analyzed. We found that allelic variants in the CYP1A1 (rs4646903), hOGG1 (rs1052133), XRCC1 (rs25487), and APEX1 (rs1130409) genes were associated with an increased level of chromosomal aberrations in workers. Informative models of gene-gene interactions including CYP1A1 (rs4646903, T>C), CYP1A2 (rs762551, C>A), GSTT1 (del); XRCC1 (rs25487, G>A), MTHFR (rs1801133, C>T), GSTT1 (del); XRCC1 (rs25487, G>A), APEX1 (rs1130409, T>G), TP53 (rs1042522, G>C) determining the formation of the increased frequency of chromosomal aberrations in the workers at coal thermal power plants were discovered.

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

We studied the effects of single nucleotide polymorphisms in the promoter regions of matrix metalloproteinase genes rs1799750 (-1607dupG) MMP1, rs243865 (C-1306T) MMP2, rs3025058 (-1171dupA) MMP3, and rs11568818 (A-181G) MMP7 on the risk of varicose vein of the lower extremities in ethnical Russians, residents of the Russian Federation. We genotyped 536 patients with this pathology and 273 healthy participants without history of chronic venous disease. Association was examined using logistic regression analysis. None of the studied polymorphisms showed statistically significant association with the risk of varicose veins of the lower extremities. Our results provide evidence that these polymorphisms are not involved in the pathogenesis of varicose veins and cannot serve as markers of predisposition to this pathology.

We analyzed the polymorphic loci in the genes of the antioxidant system enzymes, such as GSTP1 (313A>G and 341C>T), MnSOD (47С>Т), GPx1 (599C>T), and CAT (–262C>>T), among 497 residents of Kemerovo oblast (Western Siberia, Russia). The analysis of the single-locus effects demonstrated a significant protective effect of the major C allele in the GPx1 (599C>T) locus. The MDR analysis of the gene-gene interactions showed that the GPx1 and the CAT genes work in close cooperation and mutually reinforce the risk of development of squamous cell lung cancer among the inhabitants of the industrial region.

Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794). Three hundred and forty residents of the Kemerovo Region (a coal-mining region of western Siberia) were lung cancer patients exposed to air pollutants and ionizing radiation (case) and 335 were healthy donors (control). Genotyping was performed by real-time PCR and allele-specific PCR. We discovered that polymorphisms in the XPD gene in men [log-additive model: odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.17-2.31], the ATM gene in women and nonsmokers (codominant model: OR = 0.11, 95% CI: 0.02-0.49 and OR = 0.25, 95% CI: 0.08-0.72, respectively), the APEX1 gene for smokers (recessive model: OR = 2.55, 95% CI: 1.34-4.85), and the NBS1 gene for those who work in the coal industry (overdominant model: OR = 0.40, 95% CI: 0.21-0.75) are associated with an increased risk of lung cancer. Using the multifactor dimensionality reduction method, we found a model of gene-gene interactions associated with the risk of lung cancer: NBS1 (rs1805794)-XRCC1 (rs25487)-hOGG1 (rs1052133)-XPG (rs17655). These results indicate an association between combinations of polymorphisms in the studied genes and the risk of lung cancer in residents of a coal-mining region.

The aim of this study was to assess which Mycoplasma pneumoniae genotypes were present in Moscow during the years 2015-2018 and whether the proportion between detected genotypes changed over time. We were also interested in the presence of macrolide resistance (MR)Mycoplasma pneumoniae. We performed multilocus variable-number tandem-repeat (VNTR) analysis (MLVA), SNP typing, and mutation typing in the 23S rRNA gene from 117 M. pneumoniae clinical isolates. Our analysis suggests two major MLVA types: 4572 and 3562. In 2017-2018, MLVA type 4572 gradually became predominant. In general, the SNP type range is the same as described earlier for European countries. The analysis of MR mutations showed that 7% of the isolates had an A2063G mutation in the 23S rRNA gene with no isolates carrying an A2064G mutation. In 2017-2018, MLVA type 4572 (SNP type 1) begins to spread in Moscow, which was widespread globally, especially in Asian countries. SNP typing of our sample showed higher discriminatory power than MLVA typing.

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.

This paper concerns a polymorphism of the cytochrome Р450 CYP1A1 gene, the CYP1A1*2C variant (Ile462Val, rs1048943). This substitution results in the doubling of enzyme activity, which leads to the accumulation of active intermediates and increases the risk of DNA mutations and chemically induced carcinogenesis. It has been demonstrated that the 462Val allele may be a risk factor in some oncological and other multifactorial diseases. This study was carried out on Tundra Nenets of the Yamalo-Nenets Autonomous Okrug (n = 271), Nganasans in the Taimyr Peninsula (n = 186), and Russians in North Siberia (n = 267). The cohorts did not include descendants of mixed marriages. Genotyping was performed using real-time PCR with competitive TaqMan allele-specific probes. The frequency of the 462Val allele in the Tundra Nenets cohort was 23.8% (95% CI 20.4–27.6%), which corresponds to the frequency range found in East Asian populations and is higher than the values typical of Caucasoid populations. The 462Val allele frequency in the Russian cohort was 5.8% (95% CI 4.1–8.1%), which corresponds to the frequency range of Caucasoid populations. The 462Val allele frequency in the Nganasans cohort was 39.0% (95% CI 34.2–44.0%), which is higher than the frequencies found in the European, Asian and African populations. Frequencies of the 462Val variant close to that in Nganasans have been observed in Greenland’s Inuits, Native Americans, and Southern Chinese. Thus, in the populations of Tundra Nenets and Nganasans the CYP1A1 462Val allele occurs at a high frequency, greater than those typical of Caucasoid populations. A high-frequency occurrence of the 462Val allele may be indicative of a population-wide risk of diseases influenced by this genetic polymorphism, especially when the traditional mainstays are gone or previously unknown ecotoxicants appear in the areas.

Objective To investigate the association of polymorphisms located near the FOXC2 gene with the risk of varicose veins in ethnic Russians. Methods Allele, genotype, and haplotype frequencies were determined in the sample of 474 patients with primary varicose veins and in the control group of 478 individuals without a history of chronic venous disease. Results Polymorphisms rs7189489, rs4633732, and rs1035550 showed the association with the increased risk of varicose veins, but none of the observed associations remained significant after correction for multiple testing. Haplotype analysis revealed the association of haplotype rs7189489 C–rs4633732 T–rs34221221 C–rs1035550 C–rs34152738 T–rs12711457 G with the increased risk of varicose veins (OR = 2.67, P = 0.01). Conclusions Our results provide evidence that the studied polymorphisms do not play a major role in susceptibility to varicose veins development in the Russian population.

The associations of polymorphisms of the GSTM1 (del) and GSTP1 (Ile105Val) genes and smoking in a family with congenital malformations (CMs) in a newborn baby have been studied. The GSTM1 (del) and GSTP1 (Ile105Val) gene polymorphisms themselves are not associated with the risk of CMs in a newborn. However, smoking in a family may increase the risk significance of the GSTP1 (Ile105Val) genotypes in the formation of CMs in a child.

Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

The first study on the frequencies of polymorphic variants of the GSTP1 gene encoding glutathione-S-transferase P1 in Tundra Nenets and Nganasan populations was performed. The subject of the study was the single nucleotide polymorphisms rs1695 (Ile105Val substitution in the protein sequence) and rs1138272 (Ala114Val substitution) that had previously been shown to be associated with cancer and other multifactorial diseases. The data for Tundra Nenets of the Yamalo-Nenets autonomous okrug, Nganasans of the Taimyr Peninsula, and Russian residents of the Northern Siberia were compared. The frequencies of the mutant 105Val and 114Val variants were 10.8% and 0.8% in Nganasans, 23.7% and 4.8% in Nenets, and 35.8% and 9.1% in Russian population samples, respectively. The differences within all pairs of populations were significant for each allele. These differences may characterize the population-level susceptibility to cancer and other multifactorial diseases.

Varicose veins are the most common venous pathology of lower limbs. A strong body of evidence indicates a prominent role of heredity in the development of this condition, but genetic factors influencing its risk are still poorly investigated. Phenome-wide association study (PheWAS) is a novel approach to discovering associations between genetic polymorphism and multiple phenotypes. The results of the largest PheWAS today are included in the PheWAS catalog, which contains the associations with a variety of phenotypes including varicose veins of lower extremities. In our study we aimed to replicate top 5 associations from the PheWAS catalog in the population of ethnic Russians. We determined the genotypes of polymorphisms rs735854, rs7023329, rs2857595, rs6420094, and rs16856202 in the sample of 460 patients with primary varicose veins of lower extremities and 646 control subjects without a history of chronic venous disease. Though we had enough statistical power to validate the reported associations, no evidence for statistical significant association was revealed in our study. We can speculate that either these polymorphisms have no effect on the risk of varicose veins, or their effects can be modulated by currently uninvestigated ethnic, environmental or lifestyle factors.

Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing 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.

To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation. 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA). We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancer patients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancer patients harbouring the GSTM1 del polymorphism. CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.

Background. The association of GSTM1 (del) and GSTP1 (Ile105Val) polymorphisms with congenital malformations (CMs) actively studied. However, the results of various studies are conflicting. This study aims to investigate the association of GSTM1 (del), GSTP1 (Ile105Val) genetic polymorphisms and smoking in the family with congenital malformations in the newborn. Method. We studied 94 newborn with CMs and 125 healthy newborn. Null genotype of GSTM1 was identified through multiplex real-time PCR, and GSTP1 gene (Ile105Val) polymorphism was determined through TaqMan-real-time PCR. Results. The study showed that polymorphic loci of GSTM1 (del) and GSTP1 (Ile105Val) genes were not associated with the risk of congenital malformations in the newborn (P = 0,46 and P = 0,47). When comparing the frequencies of genotypes the GSTP1 (Ile105Val) gene in newborn with CMs in the families of smokers with those of healthy newborn in non-smoking families statistically significant differences between them were found (P = 0,02). The genotype Ile/Val in children was associated with CMs (ORg + f = 2,59; 95 % CI: 1,05- 6,35), while the homozygous genotype Ile/Ile in newborn was associated with a protective effect to CMs (ORg + f = 0,30; 95 % CI: 0,12-0,72). Possibly, the association of the homozygous genotype Val/Val did not reach statistical significance due to a small number of children surveyed. Conclusion. The smoking in the family increases the risk of CMs in the newborn with genotypes of GSTP1 gene (Ile105Val) polymorphism.

Methionine synthase (MTR) and methylenetetrahydrofolate reductase (MTHFR) enzymes are involved in the metabolism of methyl groups, and thus have an important role in the maintenance of proper DNA methylation level. In our study we aimed to evaluate the effect of the polymorphism A2756G (rs1805087) in the MTR gene on the level of human leukocyte genomic DNA methylation. Since the well-studied polymorphism C677T (rs1801133) in the MTHFR gene has already been shown to affect DNA methylation, we aimed to analyze the effect of MTR A2756G independently of the MTHFR C677T polymorphism. For this purpose, we collected the groups of 80 subjects with the MTR 2756AA genotype and 80 subjects with the MTR 2756GG genotype, having equal numbers of individuals with the MTHFR 677CC and the MTHFR 677TT genotypes, and determined the level of DNA methylation in each group. Individuals homozygous for the mutant MTR 2756G allele showed higher DNA methylation level than those harboring the MTR 2756AA genotype (5.061 ± 1.761% vs. 4.501 ± 1.621%, P=0.0391). Individuals with wild-type MTHFR 677СC genotype displayed higher DNA methylation level than the subjects with mutant MTHFR 677TT genotype (5.103 ± 1.767% vs. 4.323 ± 1.525%, P=0.0034). Our data provide evidence that the MTR A2756G polymorphism increases the level of DNA methylation and confirm the previous reports that the MTHFR C677T polymorphism is associated with DNA hypomethylation.

It has been suggested that DNA hypomethylation because of poorer effectiveness of the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme induces muscular growth. We hypothesised that the common, functional 1298AC polymorphism in the MTHFR gene is associated with athletic status. To test this hypothesis, we investigated the distribution of the 1298AC variant in Polish (n = 302) and Russian (n = 842) athletes divided into four groups: endurance, strength-endurance, sprint-strength and strength-endurance, as well as in 1540 control participants. We found different genotypes (the AC heterozygote advantage) and allele distributions among sprint-strength athletes and strength athletes than the groups of sedentary controls for each nationality. In the combined study, the allelic frequencies for the 1298C variant were 35.6% in sprint-strength athletes (OR 1.18 [1.02-1.36], P = 0.024 vs. controls) and 38.6% in strength athletes (OR 1.34 [1.10-1.64], P = 0.003 vs. controls). The results of the initial and repetition studies as well as the combined analysis suggest that the functional 1298AC polymorphism in the MTHFR gene is associated with athletic status. The presence of the C allele seems to be beneficial in sprint-strength and strength athletes. It needs to be established whether and to what extent this effect is mediated by alteration in DNA methylation status.

Objective Polymorphisms of glutathione S-transferase (GST) genes in mothers may be involved in teratogenesis in their offspring. This study aims to investigate the association of GST genes (T1, M1 and P1) with the risk of having children with congenital malformations (CMs) in residents of the West Siberian region of Russia. Method We studied 235 women with offspring's with CMs, and 273 women with one or more healthy children. Null genotypes of GSTM1 and GSTT1 were identified through multiplex real-time polymerase chain reaction, and GSTP1 gene (Ile105Val) polymorphism was determined through TaqMan-real-time polymerase chain reaction. Results The study showed that the maternal genotype GSTT1 «0/0» is associated with CMs in the offspring (odd ratio (OR) = 3.63, P = 5.18 × 10-9). A significant association of the maternal genotype GSTT1 «0/0» with CMs of the cardiovascular system (OR = 5.03, P = 2.93 × 10-7), urinary system (OR = 4.20, P = 3.51 × 10-6) and central nervous system (OR = 4.40, P = 6.69 × 10-5) was found in the child. No association of maternal GSTM1 (del) and GSTP1 (Ile105Val) genetic polymorphisms with CMs of the child was identified. Conclusion Homozygous deletion of the GSTT1 gene in women of the West Siberian region is a risk factor for birth defects in the child. © 2013 John Wiley & Sons, Ltd.

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".

Objective Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for monocyte, basophil, and T-lymphocyte attraction. Polymorphism rs1024611 located in the regulatory region of the MCP1 gene has previously been shown to be associated with increased MCP-1 production. In our study, we aimed to examine the association of rs1024611 with the risk of primary varicose veins (PVVs) of lower extremities. Methods The case group comprised 470 patients with PVVs, and the control group included 269 individuals without a history of chronic venous disease. All cases and controls were ethnic Russians. Genotypes were determined by real-time polymerase chain reaction allelic discrimination. Association was studied by logistic regression analysis. Results We revealed the association of genotype G/G with the increased risk of PVVs (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.02-3.44; P = .04). In the subgroup analysis, association was revealed only in patients with C2 Clinical, Etiology, Anatomy, and Pathophysiology class (allele G: OR, 1.62 [95% CI, 1.13-2.33; P = .008]; genotype G/G: OR, 3.22 [95% CI, 1.43-7.27; P = .005]), in patients with age at onset of PVVs before 30 years (allele G: OR, 1.41 [95% CI, 1.08-1.85; P = .01]; genotype G/G: OR, 2.35 [95% CI, 1.22-4.55; P = .01]), and in patients who declared no family history (allele G: OR, 1.46 [95% CI, 1.02-2.09; P = .04]; genotype G/G: OR, 2.50 [95% CI, 1.11-5.63; P = .03]). Conclusions Our results provide evidence for MCP-1 involvement in the development of PVVs and indicate that inflammation could be implicated in the pathogenesis of this condition.

Lung cancer is one of the most common forms of cancer. The aim of this study was to validate chromosome aberrations in peripheral blood lymphocytes of lung cancer patients living in a region with high air pollution and increased background radon levels as a biomarker of cancer risk. A total of 417 lung cancer patients and 468 control participants were analysed using a chromosome aberration assay in peripheral blood lymphocytes. The results showed that chromatid-type aberrations (2.26±1.58 vs. 1.60±1.58) and chromosome-type aberrations (CSAs) (0.96±1.36 vs. 0.42±0.70) in lung cancer patients were increased significantly in comparison with the controls. The most significant two-fold increase was detected for CSAs (nonsmoking patients: 0.84±1.54 vs. 0.41±0.73%, smoking patients: 0.99±1.31 vs. 0.44±0.67%). The frequency of dicentric and ring chromosomes, double minutes and rogue cells was significantly higher (P=0.002, 0.00002, 0.01, 0.0007) in the lung cancer patients. As both analysed groups lived in the same environment, our results show that increased radon levels were not the only source for the detected genome damage. Using binomial logistic regression, the estimated odds ratios and 95% confidence intervals adjusted for the main confounders (smoking, occupational exposure, age) were 1.31 (1.20-1.40) for chromatid-type aberrations, 1.28 (1.17-1.33), and 1.68 (1.49-1.88) for CSAs. It may be suggested that lung cancer patients show a significant increase in genome damage that may be caused by an interplay between exposure and individual low capacity of DNA repair, leading to genome instability.

Objective Periconceptional folate supplementation prevents a number of congenital anomalies (CA). The aim of our study was to investigate the association of 11 polymorphisms in the folate-metabolizing genes with the risk of having an offspring with CA in the Russian ethnic group. Method We genotyped 280 mothers having a CA-affected pregnancy and 390 control mothers. The most common malformations among the cases were CA of the nervous, urinary, and cardiovascular systems, and these groups were analyzed separately. Results In the whole group of CA, we revealed the associations of MTHFR C677T and MTR A2756G loci with increased risk of CA-affected pregnancy. In the group of CA of the cardiovascular system, we observed an association of MTHFR A1298C with decreased risk and an association of MTR A2756G with increased risk of CA. After the Bonferroni correction, only the association between the genotype MTR 2756GG and the risk of having a fetus with CA of the cardiovascular system remained statistically significant (OR = 4.99, P = 0.03). Conclusion These findings indicate that locus A2756G in the MTR gene may play a role in susceptibility to CA of the cardiovascular system in West Siberia, but further research is necessary to confirm the association. © 2012 John Wiley & Sons, Ltd.

Allelic variants of folate cycle enzyme genes can contribute to predisposition to cancer. The impact of polymorphic loci A2756G of MTR gene and of C1420T of SHMT1 gene for the risk of prostatic cancer was studied in residents of West Siberia. The frequency of alleles of these loci in patients (N = 371) and controls (N = 285) was determined and the data were statistically processed. No statistically significant association with prostatic cancer was detected for any of the studied loci.

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T (rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58−0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05−2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

Breast cancer is one of the most widely distributed cancers in women. We investigated the role of allele variants in the folate metabolizing genes MTHFR (C677T and A1298C alleles), SHMT1 (C1420T allele), and MTHFD (G1258A allele) as a possible factor in predisposition to breast cancer. We determined allele and genotype frequencies of single nucleotide polymorphisms (SNPs) in the case (850 women with sporadic form of breast cancer) and control (810 healthy women) groups. None of the polymorphisms were significantly associated with breast cancer risk. To increase the statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. The meta-analysis revealed no significant association between the studied SNPs and breast cancer risks either.

A major challenge presently is not only to identify the genetic polymorphisms increasing risk to diseases, but to also find out factors and mechanisms, which can counteract a risk genotype by developing a resilient phenotype. The objective of this study was to examine acquired and innate vagal mechanisms that protect against physical challenges and haemorrhages in 19 athletes and 61 non-athletes. These include examining change in heart rate variability (HF-HRV; an indicator of vagus activity) in response to orthostatic challenge, platelet count (PLT), mean platelet volume (MPV) and single-nucleotide polymorphisms in genes that encode several coagulation factors, PAI-1 and MTHFR. Individual differences in PLT and MPV were significant predictors, with opposite effects, of the profiles of the HF-HRV changes in response to orthostasis. Regular physical training of athletes indirectly (through MPV) modifies the genetic predisposing effects of some haemostatic factors (PAI-1 and MTHFR) on vagal tone and reactivity. Individual differences in vagal tone were also associated with relationships between Factor 12 C46T and Factor 11 C22771T genes polymorphisms. This study showed that genetic predispositions for coagulation are modifiable. Its potential significance is promoting advanced protection against haemorrhages in a variety of traumas and injuries, especially in individuals with coagulation deficits.

Background: Determining the allelic variants of xenobiotic biotransformation genes is important, especially for prescribing personalised drugs. Knowledge of the allele distribution in different populations may be considered when selecting the preferred medication regimen. The frequency of CYP2C9, VKORC1, CYP4F2, GGCX, CYP2D6 and CYP1A2 genes has been studied in many populations, but the populations in Central Asia have not yet been investigated. Methods and materials: Using real-time PCR and direct sequencing-based methods, the current study assessed the frequencies of 9 polymorphisms of genes encoding enzymes involved in drug metabolism in 450 healthy individuals from different regions of Kazakhstan and 575 healthy individuals from the West-Siberian region of Russia. Results: The allele frequencies in the Kazakh population were determined for CYP2C9*2 (0.02), CYP2C9*3 (0.03), VKORC1 c. 173+1369G>C, VKORC1 c. 173+1000C>T (0.72, ÐiYP4F2 (0.31), GGCX (0.04), CYP2D6*4 (0.07), CYP2D6*3 (0.01) and CYP1A2*1F (0.35). All alleles were in Hardy–Weinberg equilibrium (p > 0.05). The allele frequencies in the Russian population were as follows: CYP2C9*2, 0.08; CYP2C9*3, 0.08; VKORC1 (c. 173+1000C>T), 0.40; VKORC1 (c. 173+1369G>C), 0.41; ÐiYP4F2 (c. 1297G>A), 0.24; GGCX (c. 1913+45G>C), 0.08; CYP2D6*3, 0.15; CYP2D6*4, 0.22; and CYP1A2*1F (c. -9-154C>A), 0.31. All alleles were in Hardy–Weinberg equilibrium (p>0.05), except GGCX (p=0.04). Conclusion: The Kazakh population allele frequency was between the Caucasian and Asian populations for nearly all of the studied gene allele variants.

Superparamagnetic nanoparticles varying by their chemical composition and synthesis method were used to transfer DNA into somatic cells under the influence of constant magnetic field (method of magnetofection). Magnetite particles obtained by mechanochemical synthesis ensured higher expression of the marker gene GFP (evaluated by fluorescence intensity of the cell lysate) then particles of ferric oxide obtained by chemical co-precipitation and cobalt ferrospinel particles obtained by the mechanochemical method.

Objective To investigate the association of polymorphisms in the folate-metabolizing genes with idiopathic male infertility in a Russian population and to perform a meta-analysis. Design A case-control study. Setting Research laboratory. Patient(s) 275 men with idiopathic male infertility and a population sample of 349 men. Intervention(s) Determining the genotypes of polymorphisms MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, SHMT1 C1420T, MTHFD1 G1958A, and CBS 844ins68. Main Outcome Measure(s) Semen analyses performed according to the World Health Organization guidelines (WHO, 1999) and Kruger strict morphology test. Result(s) None of the polymorphisms were significantly associated with idiopathic male infertility after the implementation of Bonferroni correction for multiple testing, although the MTHFD1 G1958A and MTR A2756G polymorphisms showed an association before the Bonferroni correction. Meta-analysis revealed an association by use of fixed-effects model of MTHFR C677T with the risk of azoospermia. Conclusion(s) These findings suggest that polymorphisms in folate-metabolizing genes could be involved in the etiology of male infertility. Additional studies performed on larger groups are necessary to investigate the possible associations.

Polymorphisms of glutathione S-transferase (GST) genes in mothers may be involved in teratogenesis in their offspring. This study aims to investigate the association of GST genes (T1, M1 and P1) with the risk of having children with congenital malformations (CMs) in residents of the West Siberian region of Russia.We studied 235 women with offspring's with CMs, and 273 women with one or more healthy children. Null genotypes of GSTM1 and GSTT1 were identified through multiplex real-time polymerase chain reaction, and GSTP1 gene (Ile105Val) polymorphism was determined through TaqMan-real-time polymerase chain reaction.The study showed that the maternal genotype GSTT1 «0/0» is associated with CMs in the offspring (odd ratio (OR) = 3.63, P = 5.18 × 10(-9) ). A significant association of the maternal genotype GSTT1 «0/0» with CMs of the cardiovascular system (OR = 5.03, P = 2.93 × 10(-7) ), urinary system (OR = 4.20, P = 3.51 × 10(-6) ) and central nervous system (OR = 4.40, P = 6.69 × 10(-5) ) was found in the child. No association of maternal GSTM1 (del) and GSTP1 (Ile105Val) genetic polymorphisms with CMs of the child was identified.Homozygous deletion of the GSTT1 gene in women of the West Siberian region is a risk factor for birth defects in the child.

We found an alternative form of mRNA with spliced second exon (IL-4delta2 mRNA) in mouse bone marrow and splenic cells. At rest, the amount of IL-4 mRNA markedly surpassed that of IL-4delta2 mRNA. Stimulation increased the content of both mRNA forms, but the alternative variant is accumulated more intensively and rapidly. We did not detect predominance of IL-4delta2 mRNA over full-length mRNA variant in the studied mouse tissues.

Alterations in the nucleotide sequences of folate-metabolizing genes can increase the risk of malignant transformation. The aim of our study was to investigate the association of three single-nucleotide polymorphisms (SNPs) in the folate-metabolizing genes – A2756G MTR , A66G MTRR , and 844ins68 CBS – which have putative functional significance in breast cancer risk. The allele and genotype frequencies of the SNPs were determined in a case group (840 women with sporadic breast cancer) and a control group (770 women). No statistically significant association of studied SNPs with breast cancer was revealed. A meta-analysis, which included data obtained from the literature and the present research, did not reveal any statistically significant associations of these SNPs with breast cancer. The results obtained provide evidence that these SNPs are not involved in the development of breast cancer.