RESUMO
OBJECTIVE: Familial atrial fibrillation (FAF), a not uncommon arrhythmia of the atrium, is characterized by heritability, early onset and absence of other heart defects. The molecular and genetic basis is still not completely clear and genetic diagnosis cannot be achieved in about 90% of patients. In this study, we present the results of genetic screening by next generation sequencing in affected Russian families. PATIENTS AND METHODS: Sixty subjects (18 probands and 42 relatives) with a clinical diagnosis of FAF were enrolled in the study. Since AF frequently associates with other cardiomyopathies, we included all genes that were known to be associated with these disorders at the time of our study. All probands were therefore systematically screened for 47 genes selected from the literature. RESULTS: Our study revealed that seven variants co-segregated with the clinical phenotype in seven families. Interestingly, four out of six genes and three out of seven variants have already been associated with Brugada syndrome in the literature. CONCLUSIONS: To our knowledge, this is the first report of association of the CACNA1C, CTNNA3, PKP2, ANK2 and SCN10A genes with FAF; it is also the first study in Russian families.
Assuntos
Fibrilação Atrial/diagnóstico , Síndrome de Brugada/genética , Adolescente , Adulto , Anquirinas/genética , Fibrilação Atrial/genética , Síndrome de Brugada/patologia , Canais de Cálcio Tipo L/genética , Análise Mutacional de DNA , Bases de Dados Genéticas , Ecocardiografia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Linhagem , Fenótipo , Placofilinas/genética , Adulto Jovem , alfa Catenina/genéticaRESUMO
AIM: To investigate the AGTR1 A/C polymorphism associated with atrial fibrillation (AF) to form risk groups among patients who are prone to this disease. SUBJECTS AND METHODS: 90 probands with a confirmed diagnosis of AF and their 144 first-, second-, and third-degree relatives were examined. These families made up a study group. A control group was formed of 100 apparently healthy individuals without a history of cardiovascular diseases. Collection of medical history data and complaints, electrocardiography, electrocardiogram monitoring, as well as molecular genetic analysis, thyroid hormone tests were done in all the patients. RESULTS: No statistically significant data on the correlation between the AGTR1 A/C polymorphism and the development of AF were obtained in any patient subgroup. The obtained results can be due to the genetic features of a Siberian population, which are dependent on climatic conditions and geographical location, and confirm that AF is a heterogeneous disease. CONCLUSION: There were no statistically significant differences between the patients in the study group and those in the control group. Our findings suggest the heterogeneity of AF and confirm its multifactorial nature.
Assuntos
Receptor Tipo 1 de Angiotensina/genética , Adulto , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Causalidade , Eletrocardiografia/métodos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Anamnese/métodos , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Sibéria/epidemiologiaRESUMO
Chronic fatigue syndrome (CFS) is a disease that can seriously impair one's quality of life; patients complain of excessive fatigue and myalgia following physical exertion. This disease may be associated with abnormalities in genes affecting exercise tolerance and physical performance. Adenosine monophosphate deaminase (AMPD1), carnitine palmitoyltransferase II (CPT2), and the muscle isoform of glycogen phosphorylase (PYGM) genes provide instructions for producing enzymes that play major roles in energy production during work. The aim of this study was to look for evidence of genotype-associated excessive muscle fatigue. Three metabolic genes (AMPD1, CPT2, and PYGM) were therefore fully sequenced in 17 Italian patients with CFS. We examined polymorphisms known to alter the function of these metabolic genes, and compared their genotypic distributions in CFS patients and 50 healthy controls using chi-square tests and odds ratios. One-way analysis of variance with F-ratio was carried out to determine the associations between genotypes and disease severity using CF scores. No major genetic variations between patients and controls were found in the three genes studied, and we did not find any association between these genes and CFS. In conclusion, variations in AMPD1, CPT2, and PGYM genes are not associated with the onset, susceptibility, or severity of CFS.
