Association of Gene Polymorphism at Atrial Fibrillation in the Kazakh Population: Case – Control Study
Authors: Taizhanova Dana , Bazarova Nazira , Kalimbetova Akerke , Bodaubay Roza , Zholdybayeva Elena , Abylkanov Chingis 
Published: January 2025

Atrial fibrillation (AF) is the most common persistent heart rhythm disorder. The prevalence of AF increases with age. According to the GeneCards.org database, the PRRX1 gene encodes the homeodomain transcription factor that is highly expressed in the developing heart, especially in connective tissue. This suggested that the expression of the PRRX1 gene may be associated with the processes of remodeling of the left atrium, which occurs at AF. 198 persons were included in the case-control molecular genetic study. The main group included patients with AF (n=75), the control group consisted of 2 subgroups: subgroup 1 (control group 1) included conditionally healthy patients (n=73), subgroup 2 (control group 2) consisted of patients with arterial hypertension (AH) and coronary heart disease (CHD) without diagnosed AF at the time of inclusion in the study (n=50). The scientific study was approved by the Ethics Committee of Karaganda Medical University NC JSC (Protocol No. 14 dated 14.04.2020). All participants were included in the study after the informed consent signing. The study included patients with AF at the age from 26 to 84 years. The average age of patients in the main group was 66.76±9.13 (CI 64.66-68.86). 57.3% participants of the main group were male and 42.7% – female. DNA isolation was carried out in Shared Laboratory the Scientific Research Center of Karaganda Medical University NC JSC. The sampling was carried out in accordance with the standards of operational procedures (SOP) in the treatment rooms of medical organizations. 5-6 ml of whole blood was taken from the ulnar vein into vacuum tubes containing EDTA. The analysis of the rs 3903239 polymorphism of the PRRX1 gene was carried out by genotyping method based on polymerase chain reaction using CFX 96 DNA amplifier (Bio-Rad, USA), detecting in real time. In order to find the association of genes polymorphism with AF in the Kazakh population, we choose the rs 3903239 polymorphism, identified on the 1q24 chromosome of the PRRX gene. The analysis of the results was carried out using the Bio-Rad CFX Manager 2 software. The frequency of the rs 3903239 polymorphism genotypes of the PRRX1 gene in the main group and in the control groups was in the Hardy – Weinberg equilibrium. The frequency of the minor G allele occurrence in the Kazakh population corresponded to the frequency of the allele in the general population in accordance with the base 1000genome G=0.3393 (1699/5008, 1000G).
The predominant clinical and anamnestic predictors in the risk of AF development in the Kazakh population were chronic heart failure (49.3% relative to 18%; OR 4.436), age ≥ 60 years (78.6% relative to 66%; OR 1,900), coronary heart disease, in particular, myocardial infarction (26.7% relative to 20%; OR 1,455). The rs 3903239 polymorphism of the PRRX1 gene in the dominant inheritance model is associated with the risk of AF development: the frequency of occurrence of genotypes with the rare G (AG+GG) allele prevailed among patients with AF compared with the group of practically healthy patients (66.7% versus 54.8%; OR 1,650).