Polymorphic Variants Of Genes Research Articles

Predictive modeling of the probability of gynecological complications of tamoxifen therapy: A prospective study

Background. It is well known that adjuvant therapy for breast cancer (BC) with tamoxifen is associated with an increased risk of endometrial hyperplasia (EH). Currently, the problem of hyperplastic processes and endometrial cancer during long-term tamoxifen therapy is particularly relevant since the incidence of endometrial disorders has a direct correlation with the duration of tamoxifen therapy. Follow-up by a gynecologist should be tailored to consider the risk of endometrial cancer in women who survived BC to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures. Aim. To predict adverse drug reactions (ADRs) of tamoxifen, including EH, endometrial polyps, and abnormal uterine bleeding, based on mathematical modeling in relation to the carriage of polymorphic variants of cytochrome P450 enzyme genes and drug transporter proteins. Materials and methods. A prospective pharmacogenetic study of 120 women with stage I–III luminal BC receiving tamoxifen was conducted. The polymerase chain reaction method was used to detect the presence of polymorphisms of cytochrome P450 genes, followed by an assessment of their associations with ADRs of tamoxifen, namely with local gynecological symptoms. Results. Predictive models of ADR occurrence based on the logistic regression function have been created and validated by ROC analysis. We have developed a prognostic model to estimate the probability of developing a composite endpoint (polyp, EH, abnormal uterine bleeding) based on history and genetic risk factors. It was found that the predictors of the combination of local gynecological ADRs (EH, endometrial polyp, and abnormal uterine bleeding) include such factors as weight loss, the presence of asthenia, an increase in the number of births, carriage of the TT genotype of the ABCB1 3435 polymorphic variant and the GG genotype of the CYP2D6*4 polymorphic variant, GG of the CYP3A5 polymorphic variant. The relatively high incidence (43.3%) of local gynecological symptoms requires regular monitoring by obstetrician-gynecologists using instrumental methods (transvaginal ultrasound). Conclusion. This prognostic model has demonstrated high diagnostic effectiveness, which allows it to be implemented in the routine clinical practice of an obstetrician-gynecologist.

New atherosclerosis progression markers in patients with post-Chernobyl metabolic syndrome

Relevance. As an epidemiologically proven consequence of the Chernobyl NPP accident, circulatory diseases are among the leading morbidities in liquidators. To predict the development of adverse cardiovascular events in patients with metabolic syndrome, there is the ongoing search for informative laboratory markers.The objective is to show how osteopontin, osteoprotegerin, fetuin-A, and risk factors for genetic circulatory disorders are associated with traditional risk factors for circulatory disorders in Chernobyl nuclear power plant accident liquidators suffering metabolic syndrome. Another objective is to explore the perspectives to use these indicators to forecast coronary atherosclerosis progression.Methods. The study group included 50 male liquidators of the Chernobyl nuclear power plant accident who suffered metabolic syndrome. The patients were split in two groups depending on osteopontin concentration in blood serum, i.e. above or under the upper reference limit. Medical history data, biochemical parameters, including inflammatory proteins, osteoprotegerin, fetuin-A, and genotyping of polymorphic variants of genes associated with the risk of circulatory diseases were analyzed. A control group of 30 conditionally healthy men was formed to determine the normal osteopontin, osteoprotegerin and fetuin-A values in blood serum.Results and discussion. With osteopontin value exceeding 21.4 ng/mL, the liquidators’ medical history showed 1.5 times higher frequency of myocardial infarction, 2.5 times higher frequent history of acute cerebral circulation disorder; ischemic heart disease was associated with type 2 diabetes mellitus. It was shown that the group of liquidators (osteopontin over 21.4 ng/ml) was characterized by a reliable increase in atherogenicity coefficient and osteoprotegerin level. Meanwhile, when compared to the control group, the same group of patients showed lower fetuin-A values and elevated high-sensitivity C-reactive protein, homocysteine, leptin and ghrelin. It was found that in liquidators, the presence of the A allele in the vitamin B12-dependent methionine synthase (MTR) gene (2756 A>G) is associated with more pronounced biochemical markers of atherosclerosis progression compared to GG genotype carriers.Conclusion. Osteopontin performs a protective role in tissue damage, being is practically undetectable in normal conditions. However, in case of pathology its value increases dramatically. In patients with metabolic syndrome, decreased fetuin-A and osteopontin values exceeding 21.4 ng/mL require additional examination with a focus on cardiovascular pathology (coronary artery calcinosis), as well as a dual-energy X-ray absorptiometry to ensure early detection of diminished bone mineral density and body mass. It was found that in liquidators, the presence of A-allele (genotypes AA and AG) in the MTR 2756 A>G gene is characterized by deeper atherogenic changes in the lipid spectrum, increased atherogenicity coefficient and decreased adiponectin content. This justifies the need for genotyping to build individual forecast for atherosclerosis progression in this category of patients.

РАСПРЕДЕЛЕНИЕ ПОЛИМОРФНЫХ ВАРИАНТОВ ГЕНОВ ТРАНСФОРМИРУЮЩЕГО ФАКТОРА РОСТА Β1, Α1 ЦЕПИ КОЛЛАГЕНА IV ТИПА И ЭНДОТЕЛИНА-1 У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

Background. Аn important role in the development and progression of arterial hypertension (AH) is played by the influence of polymorphic variants of genes. The polymorphisms C(-509)T, T869C and G915C of the transforming growth factor β1 (TGFB1) gene, A110186299G and C110196387T of the collagen type IV α1 chain (COL4A1) gene, G5665T of the endothelin-1 (EDN1) gene can contribute to the remodeling of the arterial wall. Objective: To assess the distribution of the polymorphic variants C(-509)T, T869C and G915C of the TGFB1 gene, A110186299G and C110196387T of the COL4A1 gene, G5665T of the EDN1 gene in male patients of 30-49 years old with hypertension living in the Grodno region. Material and methods: The study included 204 men (65 healthy individuals and 139 patients with grade 1 and 2 hypertension). Survey data (general clinical examinations, genotyping by polymerase chain reaction) were analyzed using the STATISTICA 10.0 program. Results. In patients with AH and in healthy men the frequency of occurrence of the T allele of the G5665T polymorphism was 16.8% and 13.9% (р=0.45), that of the T allele of the C(-509)T polymorphism – 34.2% and 36.9% (р=0.66) respectively. The frequency of the T allele of the T869C polymorphism was 41.4% and 40.8% (p=0.99), and that of the C allele of the G915C polymorphism – 7.9% and 6.9% (р=0.84) correspondingly. The frequency of the A allele of the polymorphism A110186299G comprised 35.6% and 37.7% (р=0.74), that of the T allele of the polymorphism C110196387T – 46.4% and 43.8% (р=0.63) respectively. Conclusions. The frequency of occurrence of genotypes and alleles of the studied polymorphisms is comparable among male patients with grade 1-2 AH and practically healthy individuals.

Association of gene polymorphisms with biological features of gastric cancer

Aim of the investigation. To evaluate associations of polymorphic variants of TNF (G308A), XPC (Lys939Gln), MTHFR (Ala222Val) genes with some biological features of gastric cancer. Materials and Methods. We evaluated polymorphic gene variants in 74 patients with verified gastric cancer or gastriesophageal junction cancer (Siewert III). Genotyping was performed by DNA isolation from venous blood leukocytes of the subjects followed by PCR with electrophoretic detection of the result. The association of polymorphic variants of genes with such biological features of the tumor as localization of the process, morphological type, degree of differentiation, type of tumor growth, presence or absence of lymphovascular or perineural invasion was evaluated. Results. Lys/Gln genotype of XPC gene (Lys939Gln) are 3.3 times more likely to develop gastric body cancer (p=0.04). Genotype GG of TNF gene (G308A) 5.3 times increases the development of gastric adenocarcinoma in comparison with other histological types (p=0.018), genotype GA of the same gene 5.2 times more often develop tumor with high-grade differentiation degree (p=0.032). Val/Val genotype of the MTHFR gene (Ala222Val) are significantly less likely to develop lymphatic/vascular invasion compared to carriers of the other genotype (p=0,029). Conclusion. The obtained data suggest that the genetic status of the patient itself may affect the biological characteristics of gastric cancer, which in turn may lead to a change in the patient’s treatment tactics.

Relationship between personal anxiety and genes associated with eating disorders in women aged 45-64

Aim. To study the possible relationship between personal anxiety and polymorphic variants of genes associated with eating disorders (rs17782313 MC4R, rs1800497 DRD2, rs9939609 FTO) in women aged 45-64 in Novosibirsk.Material and methods. A random representative sample of women aged 45-64 years (n=1074, mean age, 54,27±0,2 years) was examined in 2003-2005 at the Research Institute of Internal and Preventive Medicine, a branch of the Institute of Cytology and Genetics, within the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) project. Personal anxiety was assessed using the Spielberger self-assessment questionnaire included in the protocol of the Multinational Monitoring of Trends and Determinants of Cardiovascular Disease — Optional Psychosocial Study (MONICA-MOPSY), tested at screenings of the World Health Organization (WHO) MONICA program in 1983-1995. The sample for the HAPIEE program was formed at the program data processing center in Prague for each of the collaborating centers in such a way that each respondent was random. From the sample, every second woman (n=537) was selected for genotyping of the FTO rs9939609 variant (n=384); every third woman (n=358) — for genotyping the MC4R rs17782313 (n=279) and DRD2 rs1800497 variants (n=327). Genotyping was performed in the laboratory of molecular genetic studies by the polymerase chain reaction with the analysis of restriction fragment length polymorphism.Results. Among women aged 45-64, anxiety was detected in 58,3%, and in 15,9% of women the anxiety level was high. The homozygous genotype C/C rs17782313 of the MC4R gene was more common among women with high anxiety levels (17,5%) than among women with low and moderate anxiety levels (1,8 and 0,8%, respectively; p=0,001). There were no significant differences in the detection rate of the rs1800497 genotypes of the DRD2 gene among women with different levels of anxiety (p>0,05). The frequency of the A/A rs9939609 genotype of the FTO gene was highest among women with high anxiety levels — 29,5%, compared to participants with low and moderate anxiety levels (15 and 15,3%, respectively; p=0,048). The probability of anxiety among carriers of the C/C+C/T genotypes of the MC4R gene was 1,29 times higher than among carriers of the T/T genotype (p=0,001). Among carriers of the A/A rs9939609 genotype of the FTO gene, the anxiety probability was 2,34 times higher than among carriers of the A/T+T/T genotypes (p=0,008).Conclusion. The association between anxiety and genes of eating disorders dictates the need for diagnosis and subsequent treatment of anxiety and its associated consequences.

Association of polymorphic variants of the GSTP1 and GSTM1 genes with signs of tunnel syndromes in patients with vibration disease (pilot study)

Introduction. The data on the association between GSTs gene variants and the risk of developing carpal tunnel syndrome (CTS) determine the feasibility of studying the relationship with changes in the nerve structure of the upper limbs identified by ultrasound examination in patients with vibration disease (VD). The aim of the study was to investigate the association of polymorphic variants of the GSTP1 and GSTM1 genes with signs of tunnel syndromes in VD patients. Materials and methods. Polymorphic variants of the GSTP1 (rs1695 and rs1138272) and GSTM1 genes in one hundred forty male VD patients were studied using PCR-RT method. High-resolution ultrasonography parameters were used to evaluate the morphological structure of the peripheral nerves of the upper limbs in patients, including the cross-sectional area (CSA) of the peripheral nerves. Results. A significant gain in CSA maximum of the median nerve was found in carriers of the GSTM1–/– genotype relative to those in the GSTM1+ polymorphic variant of the GSTM1 gene (p=0.014). At the same time, AG-GSTP1 (Ile105Val) heterozygote carriers were less resistant to vibration exposure compared to the AA homozygote ones. The AG carriers had a shorter period of vibration exposure (p=0.017), which was observed against the background of a pronounced tendency to a decrease in the period of vibration exposure at the time of VD diagnosis (p=0.034). Limitations. Limitations include the small number of examined patients and the analysis of associations of polymorphic variants of GSTs genes only with CSA values without taking into account the clinical and functional status of patients. Conclusion. The results obtained indicate that GSTs genes involved in protection against oxidative stress, may be associated with the development of CTS in VD patients. Further investigations are needed involving a larger number of VD patients with simultaneous analysis of the morphological structure of peripheral nerves, as well as of electrophysiological and clinical studies.

Role of gene polymorphism in the development of disorders of the lipid profile in individuals exposed to chemicals

Introduction. The prevalence of arterial hypertension and dyslipidemia in the Russian population exceeds 50%. By a number of working industrial factors have been proved to play the negative role in their development. The results of earlier studies indicate to the epigenetic role of toxic substances in relation to various genes. The aim of the study was to establish associations of polymorphic variants of cardiovascular risk genes with disorders of lipid metabolism in workers performing liquidation works in the accumulated environmental risks zone. Materials and methods. Ninety two and 82 employees from Federal Environmental Operator (FEO) and EMERCOM, respectively were studied. Parameters of lipid metabolism and polymorphic variants of APOE Cys130Arg (rs429358) and PPARG Pro12Ala (rs1801282) genes were investigated. Results. In FEO workers, each variant allele of the APOE Cys130Arg gene is associated with impaired LDL-C concentration in an additive manner (OR = 2.69; 95% CI = 1.03–7.08, p=0.04). Carrying either the T/C or C/C variant allele of this polymorphic variant or the C/G or G/G polymorphic variant Pro12Ala of the PPARG gene increases the odds of developing abnormalities in total cholesterol levels by more than 3.5-times. The risk influence of the mutant genotype G/G and allele G on the increase of Apo B concentration was also established. In EMERCOM workers, the presence of both alleles of this polymorphic variant increased the probability of a decrease in HDL-H levels by 5 times. Limitations. Male persons are employees of the FEO and the Ministry of Emergency Situations. Age accounts of 30–50 years. Conclusions. An increased risk of deviations of total cholesterol concentration, proatherogenic cholesterol, and lipoprotein fractions associated with the PPARG Pro12Ala and APOE Cys130Arg genes polymorphisms was found in FEO workers, whereas only the reduced high-density lipoprotein cholesterol risk in carriers of the PPARG Pro12Ala gene mutant allele was found in EMERCOM workers.

North India Cancer Risk: A Detailed Review with Focus on Jammu and Kashmir Demographics.

Cancer is a global medical challenge, and research is at its peak to understand the unique mechanisms of cancer cells. The expanding field of epidemiology, including molecular and environmental studies, helps us better understand the distribution of molecular changes and environmental risk factors in the population. In the present review, we aimed to find out the different genes and environmental factors that are associated with different cancers in the Jammu & Kashmir (J&K) region of the North Indian population. A Systematic approach of literature survey was used to curate research data based on genetic and environmental epidemiology specifying the J&K region. Of 640 articles found initially and screening of 490 records, 97 studies were included for the final review. It was observed that numerous genes that are strongly linked to various cancer types have been discovered as a result of the rising genotyping trend, which has grown in the demography exponentially over the last few decades. The majority of these genes are related to cell cycle regulation, cell growth signaling, and apoptosis regulation. Additionally, high promoter hypermethylation of various genes which were found to be attributed to the presence of distinct dietary patterns. The most important environmental risk attributes were salt tea consumption and dried pickles. In conclusion, the J&K population possesses many common polymorphisms in various genes with a small effect size that makes individuals more prone to different forms of cancers interacting with different environmental factors. What we can't do is, change the gene sequence or molecular changes which are the main changes for determining the susceptibility of any altered condition but what we can do is lower/ limit the exposure to the environmental factors which is a key element playing with the susceptibility's threshold. Therefore, limiting exposure to environmental factors could be a major step in lowering the risk of disease.

Genetic Predisposition to Prediabetes in the Kazakh Population.

The aim of this study was to conduct a comparative analysis of the population frequencies of the minor allele of polymorphic variants in the genes TCF7L2 (rs7903146) and PPARG (rs1801282), based on the genome-wide association studies analysis data associated with the risk of developing prediabetes, in an ethnically homogeneous Kazakh population compared to previously studied populations worldwide. This study utilized a genomic database consisting of 1800 ethnically Kazakh individuals who were considered in healthy condition. Whole-genome genotyping was performed using Illumina OmniChip 2.5-8 arrays, which interrogated approximately 2.5 million single nucleotide polymorphisms. The distribution of genotypes for the TCF7L2 (rs7903146) and PPARG (rs1801282) polymorphisms in the Kazakh sample was found to be in Hardy-Weinberg equilibrium (p > 0.05). The minor G allele of the "Asian" protective polymorphism rs1801282 in the PPARG gene was observed at a frequency of 13.8% in the Kazakh population. This suggests a potentially more significant protective effect of this polymorphism in reducing the risk of prediabetes among Kazakhs. The frequency of the unfavorable T allele of the insulin secretion-disrupting gene TCF7L2 (rs7903146) in Kazakhs was 15.2%. Studying the associations of genetic markers for prediabetes enables the timely identification of "high-risk groups" and facilitates the implementation of effective preventive measures. Further results from replicative genomic research will help identify significant polymorphic variants of genes underlying the alteration of prediabetes status.

Exploring Hepatocellular Carcinoma Pathogenesis: The Influence of Genetic Polymorphisms

Abstract: Hepatocellular carcinoma (HCC) is influenced by several factors, among which genetic polymorphisms play a key role. Polymorphisms in various genes affect key pathways involved in HCC development, including metabolism, expression of inflammatory cytokines, cell proliferation, and apoptosis regulation. These polymorphisms induce differential effects on susceptibility to HCC, disease progression, and treatment outcomes. Understanding the effect of genetic variations on HCC pathogenesis is essential to elucidate underlying mechanisms and identify potential therapeutic targets. This review explores the diverse roles of genetic polymorphisms in HCC, providing insights into the complex interplay between genetic factors and disease development.

Informative genetic markers of predisposition to the formation of high-level intelligence

This study is devoted to investigating the association of intelligence with a person’s genotype. Comparative psychological and molecular genetic testing was carried out on a representative sample of Belarusian population representatives numbering 746 people. Intelligence quotient (IQ) was determined using D. Wechsler’s test. It was established that the distribution of general intelligence values among the Belarusian population representatives was shifted towards higher results. The persons were divided into low and high IQ groups using the quartile method. The association of intelligence level with genotype was determined using a panel of genetic markers consisting of 18 gene polymorphic variants of neurogenesis, synaptic plasticity and neurotransmitter systems. Molecular genetic testing was carried out using real-time PCR. To automate a search for informative gene combinations associated with cognitive abilities, we used a special computer program that we had previously developed, taking into account the gene interaction effects. 15 most informative combinations of polymorphic gene variants associated with a high intelligence level were identified. These gene variants can be used to assess a genetic predisposition to the formation of high-level intelligence, which will allow assessing the abilities of candidates for extreme activities.

Distribution of polymorphic variants of the mannose-binding lectin gene (MBL2) in children with mild and severe asthma

Asthma is one of the most common inflammatory diseases in the world. One of the factors in the development of this disease is a low concentration of mannose-binding lectin (MBL), encoded by the MBL2 gene. Purpose. To study the distribution of genotypes and alleles of polymorphic variants of the MBL2 gene in children with asthma. Material and methods. The study included children with diagnosed bronchial asthma (n=400) (Krasnoyarsk). The control group consisted of children comparable in gender and age to the patients (n=229) and newborns (n=302). GINA-202 guidelines were used to determine the severity of the disease. Results. Statistically significant differences were identified for polymorphisms localized in the first exon of the gene – rs1800450 and rs1800451. A low occurrence of the BB rs1800450 genotype in sick and healthy children was revealed, which may be associated with early mortality or disability due to severe infections with severe MBL deficiency. Homozygotes for the mutant allele C of the rs1800451 MBL2 polymorphism were not found in any of the comparison groups, which indicates a rare distribution of this allele in Caucasian populations. Conclusion. The present study showed that polymorphisms in the MBL2 gene play a predisposing role in the development of diseases of the bronchopulmonary system using the example of asthma.

The world of top sports people – the review of genetic, epigenetic and psychological factors underlying athletic achievements in terms of neural transmission

Background: Psychogenetics of sports is a fairly recent branch that combines research on genetic, environmental, and psychological factors influencing sports accomplishments. There has been a growing interest among scientists in analysing the results of polymorphic variants of genes that code for brain neurotransmitters. Epigenetics is also significant, especially in DNA methylation in selected promoters of candidate genes. Methods: The work includes a review of the available literature on the topic. The review concerned scientific publications on cerebral neurotransmission in sports from the last 20 years.Results: The analysis of publications on the researched topic results in a holistic presentation of a new, prospective area of research: psychogenetics in sport. For biological reasons, the authors focused on the dopaminergic system, which includes catechol-methyltransferase. Epigenetics, which has been shown to significantly impact sports psychogenetics, is also central to the study.Conclusion: It has been demonstrated that elite sports development depends to some extend on a genetic component. Nevertheless, our present understanding of the molecular basis of cognitive abilities and personality traits in athletes is still insufficient and the very discipline of sports genetics and epigenetics needs further extensive research.

Clinical and pathogenetic features and polymorphic gene variants in various phenotypes of occupational bronchial asthma

Clinical and pathogenetic features and polymorphic gene variants in various phenotypes of occupational bronchial asthma

Inflammatory Response Genes' Polymorphism Associated with Risk of Rheumatic Heart Disease.

Rheumatic heart disease (RHD) caused by group A streptococcus infection is one of the most important reasons of cardiovascular morbidity and mortality in low- and middle-income countries. Aberrant host immune response modulated by polymorphisms in inflammatory response genes plays an important role in RHD pathogenesis. This study aimed to determine risk-associated polymorphic variants in inflammatory response genes in Caucasian RHD patients. A total of 251 Caucasian RHD patients and 300 healthy donors were recruited for this study, and 27 polymorphic sites in 12 genes (TLR1, TLR2, TLR4, TLR6, IL1B, IL6R, IL6, IL10, IL12RB1, IL12B, TNF and CRP) were analyzed using allele-specific PCR. It was demonstrated that the polymorphic variants rs1800871 and rs1800872 in the IL10 gene, rs 1130864, rs3093077 and rs1205 in the CRP gene, rs375947 in the IL12RB1 gene, rs 5743551 and rs5743611 in the TLR1 gene, and rs3775073 in the TLR6 gene can modify RHD risk in a gender- and age-dependent manner. The obtained results can be used to determine the personalized risk of RHD in healthy donors during medical examination or screening, as well as to develop appropriate early prevention strategies targeting RHD in the risk groups.

Genetic Features of Lipid and Carbohydrate Metabolism in Arctic Peoples.

Prolonged adaptation of ancestors of indigenous peoples of the Far North of Asia and America to extreme natural and climatic conditions of the Arctic has resulted in changes in genes controlling various metabolic processes. However, most genetic variability observed in the Eskimo and Paleoasians (the Chukchi and Koryaks) is related to adaptation to the traditional Arctic diet, which is rich in lipids and proteins but extremely poor in plant carbohydrates. The results of population genetic studies have demonstrated that specific polymorphic variants in genes related to lipid metabolism (CPT1A, FADS1, FADS2, and CYB5R2) and carbohydrate metabolism (AMY1, AMY2A, and SI) are prevalent in the Eskimo and Paleoasian peoples. When individuals deviate from their traditional dietary patterns, the aforementioned variants of genetic polymorphism can lead to the development of metabolic disorders. American Eskimo-specific variants in genes related to glucose metabolism (TBC1D and ADCY) significantly increase the risk of developing type2 diabetes. These circumstances indicate the necessity for a large-scale genetic testing of indigenous population of the Far North and the need to study the biochemical and physiological consequences of genetically determined changes in the activity of enzymes of lipid and carbohydrate metabolism.

Genetic Markers of Acute Childhood B-Lineage Lymphoblastic Leukemia in the Kazakh Population

Introduction To investigate the genetic contribution of 24 GWAS-associated polymorphic gene variants on the development of children’s B-lineage acute lymphoblastic leukemia (B-ALL) in an ethnically homogeneous population of Kazakhs. Methods A study of 205 children with B-ALL and 204 healthy children was conducted. Genotyping of polymorphic loci was carried out using the TaqMan method. Results Significant associations (p < 0.05) with the risk of childhood B-ALL were found for twelve variants, including rs6457327 of the HLA gene, rs4251961 of the IL1RN gene, and rs1800630 of the TNF gene. Carriage of the minor allele A of the protective rs1801157 polymorphism A of the CXCL12 gene reduces the risk of B-ALL in the Kazakh population by 40%. Discussion The results reveal significant associations of polymorphic genetic variants, which can serve as a basis for the development of effective methods for predicting the risk of B-ALL, early diagnosis, and timely treatment.

Associations of the TNFSF11 gene polymorphisms with knee osteoarthritis in post-menopausal women

Objective: to determine the role of the TNFSF11 gene polymorphisms rs9594738 and rs9594759 in the development of knee osteoarthritis in postmenopausal women. Material and methods. The case-control study included 483 postmenopausal women. Of these 157 were diagnosed with primary knee osteoarthritis. The remaining 326 women without signs of joint disease were included in the control group. Molecular genetic studies included determination of TNFSF11 rs9594738 and TNFSF11 rs9594759 gene polymorphisms using the real-time polymerase chain reaction. Results. Analysis of genetic markers distribution in two groups of women showed a decrease in the frequency of rs9594738 polymorphism TT genotype among the patients with osteoarthritis (odds ratio 0.59; 95% confidence interval 0.36-0.97; p=0.049). The distribution of this polymorphism alleles, as well as alleles and genotypes of TNFSF11 rs9594759 gene polymorphism in the group of women with osteoarthritis did not differ significantly from the results of the control group (p&gt;0.05). Conclusion. An association of TNFSF11 rs9594738 gene polymorphism with knee osteoarthritis in postmenopausal women has been established. Further research of TNFSF11 gene polymorphic variants role in the knee osteoarthritis etiopathogenesis are needed to develop individual approaches to the prevention and treatment of the above disease.

Search for molecular markers of joint hypermobility

Background: Joint hypermobility (JH) is a condition that can be either benign or accompanied by pain and early development of osteoarthritis. For early verification of the risk of complications, it is necessary to study the molecular pathogenesis of various JH variants. The aim of the study: The aim of this study was to search for candidate genes involved in connective tissue metabolism and causing joint hypermobility in a form isolated or combined with connective tissue dysplasia (CTD). Materials and methods: The study involved young (21,86±0,22 y.o.) people (n=181). A clinical study was conducted for the presence of signs of JH (Beighton scale) and CTD (tables Kadurina T.I.). Further, a molecular genetic study was carried out and the search for associations of polymorphic variants of genes (vitamin D receptor (VDR), lumican (LUM), tenascin (TNXB), growth/differentiation factor 5 (GDF5), magnesium ion channel TRPM6), bone morphogenetic protein type 5 (BMP5)) and JH, CTD in isolated and combined forms. Statistical data processing was carried out by comparing qualitative features using the χ2 test, Fisher's exact test, and the χ2 test with Yates' correction for contingency tables 2x2. The strength of associations was assessed in terms of the odds ratio (Odds Ratio, OR, at p&lt;0.05), the correction for multiple comparisons was carried out using the FDR method (Benjamin- Hochberg). Quantitative data were evaluated in pairs using the Student's t-test, the normality of distribution according to the Kolmogorov-Smirnov test. Results: Associations of the G allele and the GG genotype of the rs3734444 locus of the BMP5 gene with the presence of JH (OR=3.70 and OR=5.10), the A allele of the rs1470527 locus of the BMP5 gene and the presence of JH+CTD- (OR=8.00), the T allele and the TT genotype of the rs11144134 locus of the TRPM6 gene with JH in isolated (OR=3.00 and OR =10.19) and in the forms combined with CTD (OR=3.17 and OR=11.28), the TT genotype was also associated with the isolated form of CTD (OR=3.74). The GT genotype of the rs73611720 locus of the GDF5 gene was associated with isolated CTD (OR=4.15). No statistically significant associations were found for polymorphic variants rs11540149 (VDR), rs2268578 and rs3759222 (LUM), rs3130342 (TNXB). Conclusion: The G allele of locus rs3734444 of the BMP5 gene is a potential risk marker for JH in general, the A allele of locus rs1470527 is an isolated JH, the GT genotype of locus rs73611720 of the GDF5 gene is a marker for isolated CTD, the T allele of locus rs11144134 of the TRPM6 gene is a marker for JH combined with CTD.

Association of ORMDL3 single nucleotide polymorphic variants with bronchial asthma in Pathan population

BackgroundSingle nucleotide polymorphic variants of chromosome 17q21 potential candidate genes have been found to associate with asthma predisposition in many ethnically diverse populations. Identifying the potential SNPs, that are associated with asthma in a certain population, may lead to early diagnosis of genetic predisposition, thus reducing the treatment cost by timely management. This research work was planned to study the association of SNPs residing on chromosome 17q21, with asthma, in the Pathan population of Pakistan. MethodsSixty- two physician-diagnosed bronchial asthma cases and one hundred, age and gender-matched, control subjects of the Pathan ethnic group were enrolled for this study. Five SNPs from 17q21 were analyzed for their association with asthma by the Single Base Extension method using capillary-based electrophoresis. Allelic, dominant and recessive genotypic association analyses were done by PLINK and SHEsis plus version beta software, followed by Haploview v4.1 analysis of relevant haplotypes. ResultsOut of five studied SNPs, rs8076131 was significantly associated with bronchial asthma whereas rs9894164 tended to show a marginal association. Haplotype ‘TATT’ seemed to be a marginal risk factor associated with bronchial asthma in the studied population. Conclusionrs8076131 may be used as a predictive indicator of Bronchial Asthma development in risk allele carriers of Pathan ethnicity.