Polymorphic Variants Of Genes Research Articles

Association of polymorphic variants of genes of kinase signaling pathways with atypical depression

Association of polymorphic variants of genes of kinase signaling pathways with atypical depression

Lack of Associations Between PAI-1 and FXIII Polymorphisms and Arterial Ischemic Stroke in Children: A Systematic Review and Meta-Analysis.

The role of genetic risk factors for ischemic stroke seems to be in particular significance in pediatric patients. Numerous polymorphic variants of genes encoding proteins, that is, plasminogen activator inhibitor as well as coagulation factors, involved in the coagulation cascade may be related to arterial ischemic stroke (AIS) both in adults and children. We performed systematic review and 2 meta-analyses to assess possible correlations between common plasminogen activator inhibitor (PAI-1) and FXIII polymorphisms and ischemic stroke in children. We searched PubMed to identify available data published before October 2018 using appropriate keywords and inclusion criteria. Finally, 12 case–control studies were included: 8 analyzing PAI-1 polymorphism (600 children with stroke and 2152 controls) and 4—FXIII polymorphism (358 children with stroke and 451 controls). R and Comprehensive Meta-Analysis software were used to analyze the impact of the particular polymorphism in the following models: dominant, recessive, additive, and allelic. No publication bias was observed in both meta-analyses. In case of PAI-1 polymorphism, we observed no relation between 4G4G genotype of 4G allele and ischemic stroke in children. We also demonstrated lack of association between FXIII polymorphism and childhood ischemic stroke. In children with AIS, the PAI-1 and FXIII polymorphisms are not risk factors for the disease.

Polymorphic markers of certain genes in the development of dry keratoconjunctivitis in patients with rheumatoid arthritis and Sjogren's syndrome

The article reviews literature on relationships between polymorphic variants of the genes THBS1, GTF2I, MUC1, TRIM21, STAT4, PTPN22 with clinical features of dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome. The development and implementation of a method for analyzing polymorphic gene variants used to diagnose dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome will allow assessment of the possibility of developing dry keratoconjunctivitis and/or its progression in patients with autoimmune diseases or in people at risk. Determination of clinical and morphological regularities of dry keratoconjunctivitis in accordance with the revealed molecular and genetic changes will contribute to better understanding of the etiology and pathogenesis of ophthalmological manifestations of autoimmune diseases, and will also help improve the diagnostics and prognosis of dry keratoconjunctivitis.

The role of polymorphic variants of matrix metalloproteinases genes in the formation of disruption of connective tissue homeostasis and pathology of the musculoskeletal system.

A clinical assessment of the presence of osteoarthritis (OA) with various localizations, undifferentiated connective tissue dysplasia (uCTD) and joint hypermobility (JHM) in 484 individuals of both sexes of different age groups was carried out. We searched for associations of 4 polymorphic variants of matrix metalloproteinase genes (rs35068180 (MMP3), rs2252070 (MMP13) ), rs226794 and rs2830585 (ADAMTS5)) with the development of osteoarthrosis as a whole, taking into account the localization of the pathological process, the age of the patients, the ethnic origin of the study groups and the presence of undifferentiated connective tissue dysplasia as a whole and its individual phenotypic markers, as well as in the comorbid state with osteoarthritis was carried out. 158 patients had osteoarthritis, 252 had a symptom complex of uCTD, 92 of them were in the comorbid state with OA. The significance of the polymorphic loci of MMP3, MMP13, ADAMTS5 genes in the formation of the symptom complex of uCTD in general and its individual phenotypes was detected. The polymorphic locus of MMP3 gene was associated with OA in the comorbid state with uCTD. Statistically significant models based on clinical-genetic data using the method of multiple logistic regression, that allow predicting the development of osteoarthrosis of knee, hip joints and polyosteoarthrosis were calculated.

ASSOCIATION OF MATRIX METALLOPROTEINASES GENE POLYMORPHISM WITH CLINICAL MANIFESTATIONS OF BRONCHIAL ASTHMA IN CHILDREN

In the present study, we have examined association between different polymorphic variants of metalloproteinases genes and clinical manifestations of bronchial asthma in children. We observed 103 patients including 42 children with an established diagnosis of asthma. Moreover, 61 persons were examined in the control group. All patients underwent genetic testing by allele-specific polymerase chain reaction. In particular, 320A>C polymorphic locus of ММР20 gene; Val275Ala ММР20, and -8202A>G gene ММР9 were analyzed.We have found that 30 patients (71.4% of total) had bronchial asthma of mild severity, 9 children (21.4%) exhibited moderate degree, and 3 patients (7%) had severe-grade disease. Homozygous C/C variant of the polymorphic ММР20 gene, 320A>C heterozygous variant of the ММР20 Val275Ala polymorphism, and heterozygous locus of -8202A>G ММР9 gene were found to be most frequent among the children with asthma. Generally, we have observed that the frequencies of the studied alleles and genotypes did not significantly differ berween the asthma patients and children from the control group (p < 0.05). However, in patients with GGgenotype of -8202A>G ММР9 polymorphism combined with homozygosity for the C allele of ММР20 320A>C, a more severe disease was observed, being combined with polyvalent sensitization and high total IgE levels in blood serum.In conclusion, frequencies of alleles and genotypes among patients with asthma did not show any statistically significant differences from the group of healthy children. The patients homozygous for G allele of ММР9 -8202A>G polymorphism gene and for the C allele ММР20 gene (320A>C) seem to be predisposed for a more severe clinical course of the disease.

Features of antihypertensive and vasoprotective efficiency of combination of valsartan and amlodipine in patients with obesity under different polymorphic variants of CYP2C9 and CYP11B2 genes

Purpose. To evaluate the efficiency of combination antihypertensive therapy with valsartan and amlodipine in patients with arterial hypertension (AH) and obesity, depending on the polymorphisms of the CYP2C9 and CYP11B2 genes. Materials and methods. In research included 80 obese patients (body mass index ≥30 kg/m2) and AH 1-2 disease blood pressure (BP) ≥140/90 mm Hg and

Arsenic metabolites; selenium; and AS3MT, MTHFR, AQP4, AQP9, SELENOP, INMT, and MT2A polymorphisms in Croatian-Slovenian population from PHIME-CROME study

The relationships between inorganic arsenic (iAs) metabolism, selenium (Se) status, and genetic polymorphisms of various genes, commonly studied in populations exposed to high levels of iAs from drinking water, were studied in a Croatian-Slovenian population from the wider PHIME-CROME project. Population consisted of 136 pregnant women in the 3rd trimester and 176 non-pregnant women with their children (n = 176, 8–9 years old). Their exposure to iAs, defined by As (speciation) analyses of biological samples, was low. The sums of biologically active metabolites (arsenite + arsenate + methylated As forms) for pregnant women, non-pregnant women, and children, respectively were: 3.23 (2.84–3.68), 1.83 (1.54–2.16) and 2.18 (1.86–2.54) ng/mLSG; GM (95 CI). Corresponding plasma Se levels were: 54.8 (52.8–56.9), 82.3 (80.4–84.0) and 65.8 (64.3–67.3) ng/mL; GM (95 CI). As methylation efficiency indexes confirmed the relationship between pregnancy/childhood and better methylation efficiency. Archived blood and/or saliva samples were used for single nucleotide polymorphism (SNP) genotyping of arsenic(3+) methyltransferase - AS3MT (rs7085104, rs3740400, rs3740393, rs3740390, rs11191439, rs10748835, rs1046778 and the corresponding AS3MT haplotype); methylene tetrahydrofolate reductase - MTHFR (rs1801131, rs1801133); aquaporin - AQP 4 and 9 (rs9951307 and rs2414539); selenoprotein P1 - SELENOP (rs7579, rs3877899); indolethylamine N-methyltransferase - INMT (rs6970396); and metallothionein 2A - MT2A (rs28366003). Associations of SNPs with As parameters and urine Se were determined through multiple regression analyses adjusted using appropriate confounders (blood As, plasma Se, ever smoking, etc.). SNPs’ influence on As methylation, defined particularly by the secondary methylation index (SMI), confirmed the ‘protective’ role of minor alleles of six AS3MT SNPs and their haplotype only among non-pregnant women. Among the other investigated genes, the carriers of AQP9 (rs2414539) were associated with more efficient As methylation and higher urine concentration of As and Se among non-pregnant women; poorer methylation was observed for carriers of AQP4 (rs9951307) among pregnant women and SELENOP (rs7579) among non-pregnant women; MT2A (rs28366003) was associated with higher urine concentration of AsIII regardless of the pregnancy status; and INMT (rs6970396) was associated with higher As and Se concentration in non-pregnant women. Among confounders, the strongest influence was observed for plasma Se; it reduced urine AsIII concentration during pregnancy and increased secondary methylation index among non-pregnant women. In the present study of populations with low As exposure, we observed a few new As–gene associations (particularly with AQPs). More reliable interpretations will be possible after their confirmation in larger populations with higher As exposure levels.

Genetic Factors of Comorbidity of Pelvic Organ Prolapse, Stress Urinary Incontinence, and Chronic Venous Insufficiency of the Lower Limbs in Women

A genetic association study was carried out to test for a correlation between polymorphic variants of genes involved in the organization of elastic fibers (FBLN5, LOXL1, ELN, and FBN1) and multiple forms of connective tissue (CT) pathology, including pelvic organ prolapse (POP), stress urinary incontinence (SUI), and chronic venous insufficiency of the lower limbs (CVI). The FBLN5 haplotype rs12586948(A)-rs2284337(A)-rs2430347(A)-rs2430369(C), associated with a high risk for each of the studied CT disorders, was identified. For SUI and POP, common risk FBLN5 haplotype rs12586948(A)-rs2284337(A)-rs2430347(A)-rs2498841(G)-rs2018736(C)-rs2430369(C)-rs2245701(G) was detected. These allele groups, as well as the LOXL1 haplotype rs2165241(C)-rs2304719(T)-rs2415231(C), correlated with an increase in the number of coexisting connective tissue pathologies (POP, SUI, and CVI). Thus, an association between the FBLN5 and LOXL1 haplotypes and the CT disease comorbidity was identified.

Predictive Models for the Risk of Dyslipidemia in Adolescents with Essential Arterial Hypertension.

Predictive models of comorbidity, dyslipidemic disorders and essential arterial hypertension, in Russian adolescents aged 12 to 18 years (mean 15.48±1.53) were formulated with consideration for biochemical (lipid profiles) and genetic parameters (carrier state of gene polymorphic variants of apolipoprotein genes ApoA1 (-75G/A and +83C/T), ApoB (Ins/Del), ApoC3 (S1/S2), and ApoE (ε2/ε3/ε4). Significant prognostic risk factors for the mentioned comorbid pathologies were lipid metabolism parameters HDL-Ch, LDL-Ch, VLDL-Ch and carrier state of the +83T allele of the ApoA1 gene and Del allele of the ApoB gene. The obtained mathematical model is characterized by high predictive accuracy: the percentage of correct classification or the rate of correct assignment of each participant to the proper group was 96.33%.

Unfavorable variants of folate metabolism genes in patients with acute coronary syndrome in non-obstructive coronary atherosclerosis

Aim . To study the occurrence of allelic variants of folate cycle enzymes’ genes, which are unfavorable with respect to the risk of thrombophilia, to analyze the serum level of homocysteine, and to assess their impact on the development of acute coronary syndrome (ACS) in non-obstructive coronary atherosclerosis (NOCA). Material and methods . The material for the study was the results of a non- randomized, open, controlled conduct research, NCT02655718' conducted in 2015-2016 in the emergency cardiology department. The sampling included patients older than 18 years with ACS and NOCA, confirmed by invasive coronary angiography (ICAG). Patients who had previously undergone coronary artery revascularization were excluded from the study. We analyzed four polymorphic genotypes of folate cycle enzyme genes of included patients: methylene-tetra- hydro-folate-reductase MTHFR (677 C>T, 1298 A>C), methionine synthetase MTR (2756 A>G), methionine synthetase reductase MTRR (66 A>G). Determination of genotypes was performed using the methods of polymerase chain reaction and the use of a set of reagents produced by OOO “DNK-Tekhnologiya”. The level of homocysteine was determined by the enzyme immunoenzyme technique using Axis (UK) set of instruments for diagnosis and standards methods. Results . In 2015-2016 913 patients with ACS were hospitalized in emergency cardiology department; 44 (4.8%) were patients with NOKA. The mean age was 54±11 years (68% men). Mean level of homocysteine in the examined patients was 12,2 (10,8; 13,6) umol/l, in men — 12,4 umol/l (11,5; 13,6), in women — 11,3 umol/l (9,5; 13,2). Hyperhomocisteinemia (HHC) was registered in 8 (18%) individuals. The median level of homocysteine in patients with HHC was 22,8 (17,2; 25). An increase in the ultra-sensitive C-reactive protein and diagnosing of acute myocardial infarction (AMI) were more common in patients with HHC. The level of homocysteine did not differ in patients with various degrees of coronary artery stenosis; it was associated with age, hereditary background, smoking and the carriage of an unfavorable homozygous polymorphic variant of the TT genotype MTHFR gene (677 C>T). The carriage of the unfavorable TT genotype MTHFR (677 C>T) was statistically significantly more common in patients with AMI. The carriage of unfavorable homo- and heterozygous genotypes of the MTHFR gene (677 C>T) in the group without HHC was also detected. The ancestral allele C of the rs1801133 gene was statistically significantly more common in intact coronary arteries. Conclusion . In this study 96,6% of patients with ACS and NOCA were carriers of unfavorable polymorphic variants of folate metabolism genes. The carriage frequency of unfavorable T allele of rs1801133 gene is statistically significantly more common in patients with AMI. The presence of this genotype is associated with the development of HHC, which is equivalent of literature data. However, the presence of the allelic variant of TT MTHFR (677 C>T) did not always lead to the development of HHC. An increase in plasma homocysteine levels is directly proportional to age, hereditary background, smoking, and carriage of the TT rs1801133 genotype. It is also associated with an increased risk of AMI, which confirms previous studies.

The role of osteopontin in kidney diseases.

Osteopontin (OPN) is a pleiotropic glycoprotein expressed in various cell types in animals and in humans, including bone, immune, smooth muscle, epithelial and endothelial cells. Moreover, OPN is found in kidneys (in the thick ascending limbs of the loop of Henle and in distal nephrons) and urine. The protein plays an important role in mineralization and bone resorption. In addition, OPN is involved in the regulation of immunity and inflammation, angiogenesis and apoptosis. It was demonstrated that OPN and some OPN gene polymorphic variants are associated with the pathogenesis and progression of multiple disorders, such as cancer, autoimmune, neurodegenerative and cardiovascular diseases. Moreover, recent studies suggested that OPN is associated with the pathogenesis of renal failure. In this review, I briefly discussed the role of OPN and its gene polymorphisms in kidney physiology, as well as in various kidney diseases. Most studies reported that OPN expression is elevated in urolithiasis, and also in acute and chronic kidney diseases, and in renal allograft dysfunction. Moreover, it was demonstrated that polymorphic variants of the OPN gene may be associated with renal failure. However, some reports suggested that OPN is essential for tubulogenesis, and that it inhibits calcium oxalate crystal formation and retention, nitric oxide synthesis, cell apoptosis and promotes cell regeneration. Thus, further studies are required to fully understand the role of OPN in kidney physiology and pathology. Eventually, these studies may result in the identification of OPN as a valuable marker for renal dysfunction prognosis and treatment.

Analysis of frequencies of polymorphism of folate-cycle genes in women from different regions of ukraine: own study and review

The aim of this study were to analyze prevalence of the polymorphism of the MTHFR, MTRR, MTR genes in women with chronic miscarriages compared with the control population; to generalize Ukrainian data about MTHFR, MTRR and MTR genes polymorphism prevalence in women with chronic miscarriages and in general women population; to analyze impact of low-functional alleles of folate-cycle genes on processes related to the pregnancy course.To study the prevalence of polymorphic variants of the folate cycle genes, 53 patients of medical centre “Family source” with a miscarriage who had one or more spontaneous miscarriages and/or frozen/regressing pregnancies in the obstetric-gynecological history were examined. The control group 1 contained of 24 conditionally healthy women with a favorable obstetrical anamnesis (absence of spontaneous abortions, complications of pregnancies and childbirths). As a control group 2 was used comparison group from the study of SI “Institute of hereditary diseases of the NAMS of Ukraine” (Lviv) – 150 women of the Western region of Ukraine without complicated genetic and obstetric history who had two or more healthy children. All groups were similar in terms of basic demographic characteristics.Results and сonclusions. A significant percentage of women with low-functional alleles in one, several or all genes MTHFR, MTRR, MTR, was found 83% (44 of 53 studied women of main group). The genotype frequencies of these genes in patients with miscarriages were compared with population control groups from Ukraine. According to data from different regions of Ukraine, the mean frequency of low-functional polymorphic variants of gene MTHFR С677->Т exceeds 50% in the general women population. The relation/association of low-functional alleles of genes MTHFR, MTRR, MTR with disorders of various processes associated with the pregnancy course was considered.

Celiac disease and endocrine autoimmunity - the genetic link.

Celiac disease is a small intestinal inflammatory disease with autoimmune features that is triggered and maintained by the ingestion of the storage proteins (gluten) of wheat, barley and rye. The prevalence of celiac disease is increased in patients with monoglandular and/or polyglandular autoimmunity and their relatives. Between 10 and 30% of patients with celiac disease are thyroid and/or type 1 diabetes antibody positive, while around 5 to 7% of patients with autoimmune thyroid disease and/or type 1 diabetes are IgA anti-tissue transglutaminase antibody positive. The close relationship between celiac disease and endocrine autoimmunity is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and/or DQ8 (DQA1*0301-DQB1*0302), that are tightly linked to DR3 and DR4, respectively, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms of various genes that are involved in immune regulation have been identified as "overlap" susceptibility genes for both celiac disease and monoglandular or polyglandular autoimmunity. While plausible, it remains to be established how far a gluten free diet may prevent or ameliorate glandular autoimmunity. In conclusion, all patients with celiac disease should be screened for type 1 diabetes and/or autoimmune thyroid disease. Conversely, patients with the above autoimmune endocrine disorders should be also screened for celiac disease.

To investigate the affiliation of XRCC-1 Gene Arg194Trp polymorphism in alcohol and tobacco substance users and loco-regionally progressed Laryngeal squamous cell carcinoma

ObjectivesThe correlation of XRCC-1 Gene Arg194Trp polymorphism with alcohol and tobacco substance user and with loco-regionally progressed squamous cell cancer of the larynx (LSCC) was assessed in this research study. The result of this research study is described herein. Material and methodsA tertiary hospital-based observational case-control research was carried out. DNA segregation and Genotype examination were done from the blood sample of the control group and cases to know the correlation between XRCC-1 gene polymorphism with loco-regionally progressed LSCC and with hazard factors tobacco and alcohol. ResultsIn the cases, the existence of DNA repair XRCC-1 gene polymorphic variants (Hetero CT and Mutant TT) was recognizable in contrary to the control group arm. The XRCC-1 gene polymorphic hetero (CT) genotype (O.R-1.96; 95% C.I: 1.23–3.13; P < 0.004) and mutant (TT) genotype variants (O.R-1.95; 95% C.I: 0.59–6.44; P = 0.27) was correlated with access hazard of loco-regionally progressed LSCC, and its statistically convincing for polymorphic hetero (CT) variant. The data were adapted for the age of the patients and control group, circadian alcohol intake, tobacco chewing habits, and the tobacco smoking habits during application of multivariate logistic regression. Its apparent that the hazard is amalgamated with hetero (CT) genotype variant (O.R- 1.67; 95% C.I: 0.98–2.82; P = 0.05) and mutant (TT) genotype variant (O.R- 1.62; 95% C.I: 0.88–2.78; P = 0.11) and its statistically convincing for polymorphic hetero (CT) genotype variant. Cases with the record of substance use (alcohol and tobacco) have an abundance of XRCC-1 hetero (CT) and mutant (TT) genotype variants in allegory to control group. Increased hazard is related with XRCC-1 hetero (CT) variant in smokers (O.R 3.28; 95% C.I: 1.45–7.41; P = 0.004), in tobacco chewers (O.R-3.79; 95% C.I: 1.87–7.71; P = 0.0002), and in alcohol consumers (O.R- 4.24; 95% C.I: 2.21–8.15; P= <0.0001) which is statistically significant. ConclusionThis research investigation demonstrates the correlation of XRCC-1 polymorphic hetero genotype (CT) & mutant genotype (TT) variants as hazard factor in loco-regionally progressed LSCC. Cases with the record of alcohol intake habits, tobacco smoking and chewing habits and XRCC-1 hetero genotype (CT) variant have statistically increased the hazard of loco-regionally progressed LSCC, which demonstrate the role of gene-ecological interconnection in modifying the vulnerability of loco-regionally progressed LSCC.

Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study

AimTo analyze the distribution of SLC6A4 gene polymorphisms in Crohn’s disease (CD) patients and their association with the disease.MethodsWe evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis.ResultsCD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P = 0.154) and age (41.3 ± 12.8 years vs 41.7 ± 8.8 years, respectively, P = 0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P = 0.003 and P = 0.002, respectively) and between the corresponding female subgroups (P = 0.004 and P = 0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P = 0.013, age- and sex-adjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P = 0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P = 0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes.ConclusionSTin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis.

IMMUNOLOGICAL AND GENETIC CHANGES AS PREDICTORS IN THE LOSS OF PREGNANCY IN THE FORMATION OF RETROCHORIAL HEMATOMA IN THE FIRST TRIMESTER

Background. Pregnancy with a retrochorial hematoma in a third of cases ends prematurely. Detection of early markers of pregnancy loss is extremely necessary for the prevention and therapy of miscarriage.Aims. The aim of the study is development and pathogenetically substantiation a new diagnostic algorithm in the formation of retrochorial hematoma in the first trimester of pregnancy.Materials and methods. A prospective study of women of reproductive age with retrochorial hematoma applied at the gestational age of 6–12 weeks was performed. A study was made of polymorphic variants of genes of hemostasis system; the folate cycle by polymerase chain reaction. The level of embryotropic antibodies was determined by the ELI-P-Complex-12 system test. The course of pregnancy and delivery was monitored.Results. The study involved 113 women. There was no correlation between the isolated carrier of polymorphisms and an increased risk of pregnancy loss (p ˃ 0.05). Polymorphic variants of genes of hemostasis system; the folate cycle in combination with an increase in the level of rheumatoid factor or autoantibodies to thyroglobulin have a relationship with the risk of miscarriage (р ˂ 0.05).Conclusion. Polymorphic variants of genes of hemostasis system; the folate cycle in combination with an increase in the level of rheumatoid factor or autoantibodies to thyroglobulin are predictors of an unfavorable outcome of pregnancy. Therefore; the definition of these markers can be used for individualization of the survey; treatment at the precognitive stage and during pregnancy.

ФИЗИОЛОГИЧЕСКИЕ МЕХАНИЗМЫ ГЕНЕТИЧЕСКОЙ РЕГУЛЯЦИИ ФУНКЦИОНАЛЬНОЙ РАБОТОСПОСОБНОСТИ И ВЫНОСЛИВОСТИ ОРГАНИЗМА СПОРТСМЕНОВ-ЕДИНОБОРЦЕВ ПРИ АДАПТАЦИИ К ФИЗИЧЕСКОЙ НАГРУЗКЕ

Aim. The article deals with studying physiological mechanisms of the polymorphic variants of genes H1F1A Pro/Ser, influencing adaptation in combat athletes during physical load. Materials and methods. We studied combat athletes of various ranks from a sports school in Chelyabinsk: athletes of 1st, 2nd, and 3rd ranks (youth ranking) – 23 persons (control group); athletes of 1st, 2nd, and 3rd ranks (adult ranking) – 27 persons (experimental group 1); professional athletes (Candidate for Master of Sport and Master of Sport) – 26 persons (experimental group 2). We studied polymorphic variants of genes, regulating the cardiovascular system, performance, and endurance in combat athletes (HIF1A Pro/Ser). We performed the amplification of the fragments of genomic DNA, containing polymorphic parts, by polymerase chain reaction (PCR) in iQ5 Bio-Rad (the USA) and GeneAmp PCR System 9700 (Applied Biosystems, the USA) amplifiers. Primers were synthesized by Evrogen company (Russia). Results. During the typing of Pro582Ser polymorphism of H1F1A gene, we revealed three genotypes and two alleles. Only in the experimental group 2, H1F1A *Ser/Ser genotype has a frequency of 76.47%; for the same sample, the frequency of H1F1*Ser allele is 87.2% and of H1F1A*Pro allele is 12.75%. Conclusion. We performed the analysis of the polymorphic loci of molecular genetic markers (HIF1A Ser/Ser, HIF1A*Ser). This allowed us to determine the cardiorespiratory and aerobic glycolytic system performance in wrestlers during their adaptation to physical load. Our analysis revealed that there is a direct correlation between the high level of integral functional preparedness in combat athletes and athletes’ gene alleles (HIF1A Ser/Ser, HIF1A*Ser). To achieve success in combat sports, the optimal number of these alleles is from 4 to 6.

Association of Leptin Gene (LEP) Polymorphism with Growth Rates and Milk Production in Holstein First-Calf Heifers

The objective of the work is to study the polymorphic leptin gene variants and their influence on growth, development, and milk production of Holstein first-calf heifers, whose 172 blood samples were analyzed. Genotyping the leptin gene locus was performed with the PCR-RFLP method. The frequencies of occurrence of the C and T alleles comprised 0.62 and 0.38, respectively; the values for genotypes CC, TC, and TT comprised 35.5% (61 animals), 53.3% (90 animals), and 12.2% (21 animals), respectively. It was ascertained that the analyzed animal population is in the genetic balanced equilibrium state according to the Hardy–Weinberg law. Under similar conditions of feeding and nutritional supplement, the animals having genotype CC were significantly superior to their peers with the other genotypes in all the parameters characterizing the live weight at different ages. However, the milk yield, the fat mass fraction, the milk fat yield, and the milk protein yield in the specimens having the TT genotype were higher by 8.9% (P ≤ 0.01; 673.4 kg), 0.20, 12.9% (P ≤ 0.05; 38.4 kg), and 9.0% (P ≤ 0.05; 22.7 KG), respectively, than that in the genotype TC carriers. The coefficient of milkability was 142.1 kg higher in all the first-calf heifers when compared to the lower value for the entire herd, therefore, indicating the specific dairy type of the analyzed animal population. The obtained data can prove the associations between the different genotypes of the leptin gene and the growth rates, the physical development, and the milk production in Holstein cattle.

Ethnic and Geographical Aspects of the Prevalence of the Polymorphic Variants of Genes Associated with Tuberculosis

Specificity of the structure of gene pools of different ethno-territorial groups of the human population can underlie the epidemiological features of the spread of tuberculosis (TB) and the structure of the genetic component of the susceptibility to the disease. The variability of 62 genetic variants potentially associated with the risk of the development of TB in the Russian population of the city of Tomsk has been studied and the differentiation of various ethno-territorial groups of the world by these markers has been assessed. The studied sample comprised 445 Russian residents of the city of Tomsk without bronchopulmonary pathology. For comparison, the data on the variability of the genetic markers of interest in 26 populations from the 1000 Genomes Project was involved. In the Tomsk population, only the ancestral allele was found for seven of the 58 SNPs studied; the allele frequencies for 36 markers were within the limits of the values seen in other European populations; for 12 SNPs, the observed frequencies were closer to populations with a significant Mongoloid component. By the total of the SNPs, the Tomsk population, despite the geographical distance from the rest of the European populations, did not differ from them (in genetic distances and Gst statistics), although it had some features of the gene pool. Intergroup differentiation of the world populations by these SNPs reflects mainly interracial differences. The greatest differences in the genetic structure between the studied populations were seen for the markers localized in intergenic regions. Statistically significant differences were found when comparing the levels of the average expected heterozygosity between groups of “L4 carrier populations” of mycobacteria and “non-L4” populations, which indicates the impact of the prevalence of different pathogenic lineages of M. tuberculosis on the formation of population specificity of the allelic frequencies.

Search for associations of polymorphic variants of nucleotide excision repair genes with the increased risk of bronchopulmonary pathology in workers of hazardous and dangerous industries

The study covered workers of asbestos cement plants and miners (n = 214). Polymerase chain reaction method in real time helped to identify genotypes of genes XPD (rs13181, rs799793) and ERCC1 (rs11615).The study results prove that XPD*C/C genotype is associated with bronchopulmonary disease risk (p≤0.02, χ2=4.97; OR=2.40; 95% CI: 1.03–5.64).Carriers of XPD*A/C genotype appeared to have relative resistance to bronchopulmonary diseases risk (χ2=3,52, р≤0,06; OR=0,57; 95%CI: 0,30–1,07).