Carriers Of Homozygous Genotype Research Articles

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the А allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men.

Association of ADRB1 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1801252 polymorphism of the ADRB1 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A145G polymorphism of the ADRB1 gene (rs1801252 ). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 70.3% of patients were carriers of the common homozygous A145A genotype, the heterozygous A145G genotype-27.0%, and the rare homozygous G145G genotype-2.7%. In the control group 71.9% of patients were identified as carriers of a homozygous genotype by a common allele, and 25.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 2.7%. Statistical analysis showed no achievement of statistical significance level across any of the genotypes. In the group with DM IG, there was no association with the rs1801252 polymorphism of the ADRB1 gene. Conclusion A statistically significant association of rs1801252 of the ADRB1 gene with DCMP was not found. The association of DM IG c rs1801252 could not be confirmed.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1042713 polymorphism of the ADRB2 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 16 AG polymorphism of the ADRB2 gene (rs1042713). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 10.8% of patients were carriers of the common homozygous 16AA genotype, the heterozygous 16AG genotype-48.6%, and the rare homozygous 16GG genotype-40.5%. In the control group 11.8% of patients were identified as carriers of a homozygous genotype by a common allele, and 47.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 40.7%. The analysis non revealed a statistically significant decrease in the frequency of carrying the homozygous 16GG genotype in patients with DCMP compared to the control group of the rs1042713 polymorphism of the ADRB2 gene. In the group with DM IG, there was no association with the rs1042713 polymorphism of the ADRB2 gene. Conclusion A statistically significant association of rs1042713 of the ADRB2 gene with DCMP was not found. The association of DMI c rs1042713 could not be confirmed.

Association of CTLA4 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs231775 polymorphism of the CTLA4 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 49A/G polymorphism of the CTLA4 gene (rs231775). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 34.2% of patients were carriers of the common homozygous 49AA genotype, the heterozygous 49AG genotype-48.6%, and the rare homozygous 49GG genotype-17.1%. In the control group 33.5% of patients were identified as carriers of a homozygous genotype by a common allele, and 49.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 17.2%. The analysis revealed a statistically non significant increase in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs231775 polymorphism of the CTLA4 gene. In the group with DMI, there was no association with the rs231775 polymorphism of the CTLA4 gene. Conclusion A statistically significant association of rs231775 of the CTLA4 gene with DCMP was not found. The association of DMI c rs231775 could not be confirmed.

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim. To evaluate the Association of rs1805124 polymorphism of the SCN5A gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods. The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs 1805124). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results. In the group with DCMP 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group with DM IG, there was no association with the rs1805124 polymorphism of the SCN5A gene. Conclusion. A statistically significant Association of rs1805124 of the SCN5A gene with DCMP was found. The Association of DM IG c rs1805124 could not be confirmed.

Germline Genetic Variants of the Renin-Angiotensin System, Hypoxia and Angiogenesis in Non-Small Cell Lung Cancer Progression: Discovery and Validation Studies.

Simple SummaryThe presence of polymorphic gene variants in the human genome provides extensive genetic (and eventually phenotypic) variation affecting both normal physiological mechanisms and cancer pathogenesis. Functional genetic polymorphisms might have predictive and/or prognostic value in lung cancer, opening novel opportunities to improve prediction and guide clinical reasoning and therapeutics in lung cancer patients. Recent knowledge pinpoints a pleiotropic role for renin-angiotensin system, particularly in the lung and mainly through locally regulated alternative molecules and secondary pathways. Dysregulation of this system play a role in cell proliferation, hypoxia and angiogenesis, which processes are involved in lung cancer progression. Here we suggest that polymorphic variants in genes coding for renin-angiotensin system might play a role in Non-Small Cell Lung Cancer progression.Introduction: The renin–angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. Methods: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. Results: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2–0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2–2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2–3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3–6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. Conclusion: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC.

The rs7574865 polymorphism of the <i>STAT4</i> gene and risk of early rheumatoid arthritis development (the REMARKA study)

The aim of the study was investigation of association of the rs7574865 polymorphism of STAT4 gene (Signal Transducer and Activator of Transcription 4, a family of signal transduction and transcription activation molecules 4) with very early rheumatoid arthritis (RA) in Russian patients, and the study of the relationship of "phenotype – genotype", particularly of positivity for antibodies to cyclic citrullinated peptides (ACCP), their concentration, the presence of erosive joint damage at inclusion in patients the study with the STAT4 gene polymorphism. Material and methods. The study was conducted in the framework of the program REMARKA (Russian study of Methotrexate and biological drugs in Early active Arthritis). 85 patients with very early RA with a duration of symptoms no more than 6 months, not receiving disease modifying anti-rheumatic drugs (DMARD) and biologicals were included. Results and discussion. The analysis of the distribution of genotypes and alleles of STAT4 rs7574865 polymorphism showed that the frequencies of g/G, G/T and T/T genotypes differ at the level of the prominent tendency to statistical significance between patients with RA and the control group (p=0.05). The frequency of minor allele T in RA is significantly higher than that in the control group, and this allele is associated with a predisposition to RA [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.1–2.8; p=0.03]. In the study of the "genotype – phenotype" relationship, STAT4 gene polymorphism correlated with erosive joint damage (r2=0.289; p=0.008). In carriers of the homozygous genotype TT, the number of erosions at inclusion in the study was significantly higher compared with carriers of genotypes GG/GT (median 5.50 [0.754; 7.5] and 0.00 [0.00; 2.00], respectively; p=0.003). The risk of erosion is also associated with the polymorphism of the STAT4 gene (OR 8.6; 95% CI 1.0–204.9; p=0.03). A difference of the ACCP level depending on STAT4 gene polymorphism was revealed: carriers of at least one minor allele T (G/T+T/T) had significantly higher concentration of ACCP than that in carriers of homozygous GG genotype: 248.97±151.00 and 179.51±147.01 U/ml, respectively; p=0.048).Conclusion. The study showed that in Russian patients with very early RA, the STAT4 gene rs7574865 polymorphism is associated with both predisposition to the disease and prognostically unfavorable manifestations (phenotypes) of the disease, namely, with the development of erosion in the early stages of the disease and an increase of the ACCP level.

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population

Objective: The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.Methods: The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5th, 7th, 10th, and 15th year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.Results: We found that carriers of homozygous genotype for alleles DRB1*15 and DQB1*03 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB1*03/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5th year of disease duration was found in carriers of DRB1*07 allele (p cor = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p cor = 0.0305).Discussion: We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB1*15/15 and DQB1*03/*03 were identified as short-term clinical negative prognostic factors, while allele DRB1*07 carriage appeared to be a positive prognostic marker of better MS outcome.

CHARACTERISTICS OF UKRAINIAN GREY CATTLE BY DNA-MARKERS

CHARACTERISTICS OF UKRAINIAN GREY CATTLE BY DNA-MARKERS