Haplotypes of NOS3 Gene Polymorphisms in Dilated Cardiomyopathy (original) (raw)
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Genetics and Molecular Research, 2019
The eNOS Glu298Asp (rs1799983) polymorphism of the NOS3 gene has been implicated as a risk factor for cardiovascular diseases; however, not all studies find significant associations. We examined this possibility in a Russian (Siberian) population. One hundred patients with chronic heart failure and 40 controls were investigated. PCR analysis was performed on DNA samples. The aim was to evaluate a possible association between the (Glu298Asp) polymorphism (rs1799983) of the NOS3 gene and susceptibility to chronic heart failure in the Russian population. We evaluated genotype distributions in patient and control groups and assessed the relationship between genotypes and chronic heart failure. We found that this polymorphism is not associated with increased risk of chronic heart failure in our study cohort. In conclusion, testing of the NOS3 gene polymorphism does not seem useful for evaluating predisposition for chronic heart failure or its diagnosis and prognosis.
Circulation Journal, 2021
were scarce. With next-generation sequencing, multiple genes can be analyzed simultaneously, making genetic testing a powerful tool for disease management as for hypertrophic cardiomyopathy (HCM). However, the clinical utility of DCM genetic testing still needs to be established. Furthermore, a focused panel comprising the most prevalent DCM-associated genes in the Vietnamese population would enable a cost-effective DCM genetic testing program in Vietnam. Our study aimed to determine the prevalence of rare variants from 58 DCM-related genes in 230 well-phenotyped DCM Vietnamese patients, and to analyze genotype-D ilated cardiomyopathy (DCM) was characterized by left or biventricular dilatation and systolic dysfunction in the absence of secondary causes such as coronary artery disease. 1 With a prevalence of 1 in 250 in the population, DCM is a common cause of heart failure and the leading indication for cardiac transplantation. 2 DCM can be attributed to genetic and non-genetic causes, with approximately 40% of DCM cases having a genetic cause. 3 Rare variants in multiple genes encoding cardiac sarcomeric, cytoskeletal, desmosomal, nuclear lamina, mitochondrial and ion flux-handling proteins have been linked to disease manifestations. 4 The relationship between mutations in DCM-related genes and abnormalities of cardiac morphology and functions were investigated mostly in Western populations; data from Asian countries
Genetics and Molecular Research, 2019
The eNOS Glu298Asp (rs1799983) polymorphism of the NOS3 gene has been implicated as a risk factor for cardiovascular diseases; however, not all studies find significant associations. We examined this possibility in a Russian (Siberian) population. One hundred patients with chronic heart failure and 40 controls were investigated. PCR analysis was performed on DNA samples. The aim was to evaluate a possible association between the (Glu298Asp) polymorphism (rs1799983) of the NOS3 gene and susceptibility to chronic heart failure in the Russian population. We evaluated genotype distributions in patient and control groups and assessed the relationship between genotypes and chronic heart failure. We found that this polymorphism is not associated with increased risk of chronic heart failure in our study cohort. In conclusion, testing of the NOS3 gene polymorphism does not seem useful for evaluating predisposition for chronic heart failure or its diagnosis and prognosis.
Cardiovascular research, 2018
Dilated cardiomyopathy (DCM) frequently affects relatively young, economically, and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance-malignancy of the mutated gene-but also on epigenetics, age, toxic factors, pregnancy, and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN), or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular ass...
Circulation: Heart Failure
Background: It was the aim to investigate the frequency and genetic basis of dilated cardiomyopathy (DCM) among relatives of index patients with unexplained heart failure at a tertiary referral center. Methods: Clinical investigations were performed in 109 DCM index patients and 445 of their relatives. All index patients underwent genetic investigations of 76 disease-associated DCM genes. A family history of DCM occurred in 11% (n=12) while clinical investigations identified familial DCM in a total of 32% (n=35). One-fifth of all relatives (n=95) had DCM of whom 60% (n=57) had symptoms of heart failure at diagnosis, whereas 40% (n=38) were asymptomatic. Symptomatic relatives had a shorter event-free survival than asymptomatic DCM relatives ( P <0.001). Results: Genetic investigations identified 43 pathogenic (n=27) or likely pathogenic (n=16) variants according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Forty-fou...
American Heart Journal, 2005
Background In addition to its well-recognized role in the regulation of vascular tone, nitric oxide modulates sympathetic and parasympathetic nervous system activities. Abnormalities of both autonomic control and nitric oxide synthase activity are known to occur in patients with congestive heart failure. Recently, a polymorphism of the promoter of the endothelial nitric oxide synthase (eNOS) gene has been associated with a reduction of eNOS activity. This study tested the hypothesis that patients with congestive heart failure who are homozygous for this polymorphism will have a more advanced imbalance of autonomic activity.
Genetic polymorphisms and heart failure
Genetics in Medicine, 2004
Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.
Journal of Cardiac Failure, 2010
Background-Alterations of endothelial nitric oxide synthase (eNOS) enzyme activity via eNOS gene polymorphisms have been associated with significant cardiovascular morbidity and mortality. Both the thymidine to cytosine transition mutation (T −786 →C) in the promoter region and the missense mutation in the exon 7 coding region of the eNOS gene (G 894 →T) have been associated with several cardiovascular disease states. We hypothesized that heart transplant recipients who carried at least one allele of either of the polymorphisms would have reduced myocardial tissue expression of eNOS measured in the explanted heart. Methods/Results-Genomic DNA was isolated from myocardial tissue samples obtained from 43 explanted human hearts using standard methods. Regions of the eNOS gene were amplified from genomic DNA with a polymerase chain reaction using specific primers. Protein expression of eNOS was measured by Western blot analysis. There was a statistically significant decrease in mean eNOS
Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy 
Research Square (Research Square), 2020
Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identi ed mutations. Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with con rmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a signi cantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial brillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was signi cantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral lea et abnormalities (40% vs. 19%; p=0.039). Calci cations of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079). Conclusions: Major ndings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.