Genetic markers of atrial fibrillation in patients with hypertension in combination with non-cardiac diseases
Authors: Hidirova L. D. , Yakhontov D. A. , Zenin S. A. , Maximov V. N. 
Published: July 2019

<p><strong>Letter to the editor:</strong></p><p>The world medical community has categorised atrial fibrillation (AF) as one of the three cardiovascular ‘epidemics of the 21st century’, along with chronic heart failure and diabetes mellitus [1]. In recent years, the prevalence of AF has increasing steadily. However, the exact cause for the increase in the incidence of AF<br />cannot be explained only by the increase in life expectancy, prevalence of cardiac valve disease or prevalence of myocardial infarction [2].</p><p>Although AF occurs in individuals with various manifestations of coronary heart disease, it is increasingly being diagnosed in patients with arterial hypertension without coronary heart disease [3]. AF causes serious cardiovascular complications; thus, a deep understanding of its pathogenetic aspects and a comprehensive study that considers comorbid pathologies for identifying the predictors of the development and progression of AF are required [4].</p><p>Hereditary factors can play a significant role in the development of AF and hypertension; consequently, the worldwide practice of scientific research in basic medicine pays significant attention to the molecular genetics methods of analysis.</p><p>This study aimed to evaluate the genetic determinants in patients with hypertension with AF progression accompanied by various extra-cardiac comorbid pathologies.</p><p>This prospective cohort study included 167 patients with a paroxysmal and persistent form of AF and stage III hypertonic disease without coronary heart disease. The average age of the patients was 53.3 ± 7.1 years. DNA isolation from blood leucocytes was performed using phenol–chloroform extraction. The rs1378942 polymorphism of the CSK gene, the rs220073 polymorphism and the -174G/C polymorphism (rs1800795) of the IL6 gene were assessed using polymerase chain reaction-restriction fragment length polymorphism. The statistical hypotheses were considered significant at a critical level of p = 0.05, i.e.<br />the difference was considered statistically significant at p &lt; 0.05. The lower limit of evidentiary power was equal to 80%.</p><p>This study reported associations between the rs1378942 polymorphism of the CSK gene, the rs1800795 polymorphism of the IL6 gene and the rs220073 polymorphism and the progression of AF in combination with the following associated diseases: hypertension, chronic obstructive pulmonary disease, hypothyroidism, type 2 diabetes mellitus and abdominal obesity. The relative risk of the progression of AF in carriers of the allele C was 1.94 times higher than that in carriers of the allele A [95% confidence interval (CI), 1.21–3.09]. Carriage of the AA genotype was conditionally protective against the progression of AF (relative risk, 0.41; 95% CI, 0.21–0.80; p = 0.010).</p><p>Associations of the rs1378942 and rs1800795 polymorphisms with the risk of recurrence of AF in combination with certain diseases were also found. In addition, associations were identified between rs1378942 and glomerular filtration rate, systolic and diastolic blood pressure, left atrial wall thickness and glucose, high-density lipoprotein (HDL) cholesterol, triglyceride and creatinine levels; between rs220073 and levels of triglycerides, atherogenic index, creatinine, fibrinogen and the number of months before the development of relapse and between rs1800795 and HDL cholesterol, creatinine and galectin-3 levels and diastolic blood pressure.</p><p>The secondary form of AF as a multi-factorial disease develops under the influence of many factors of both the external environment and hereditary nature. The complexity of the etio-pathogenesis of the disease makes it extremely difficult for researchers to identify the factors that play a leading role in the development of the pathological process. Currently, associative studies of AF with polymorphisms of &gt;260 genes have been conducted, and genome-wide associative studies have been performed as well. The reproducibility of the results depends on several factors: age, sex, comorbidities, ethnicity, penetrance, expressiveness, pleiotropy, various epigenetic influences and many more.</p><p>Despite the limitations of the sample, our study adds to the data material already available that can serve in the prognostic assessment of the development and progression of AF. Further studies will allow the development of a personalised algorithm for predicting the progression of AF in hypertension combined<br />with extra-cardiac diseases. In this regard, further larger studies are necessary that involve other institutions and a larger sample of patients, which will make it possible to predict the progression of AF with the definition of additional molecular criteria for evaluating the effectiveness of pathogenetic therapy and the possibilities of targeted treatment.<br /><strong></strong></p><p><strong>Funding:</strong> The study did not have sponsorship.<br /><strong></strong></p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p>