The 4q25/PITX2 SNP rs6817105 and Atrial Fibrillation in Uzbek Patients with Arterial Hypertension

Abstract

Background: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and a major predictor of morbidity and mortality. In recent years, genome-wide association studies (GWAS) have identified common genetic variants associated with a higher risk of AF. The aim of our research was to study the possible association of the 4q25/PITX2 SNP rs6817105 with the risk of developing AF in patients with arterial hypertension (AH) in the Uzbek population. Methods and Results: The study included 142 AH (Grades 1-3; ESC/ESH, 2018) patients of Uzbek nationality who were initially diagnosed with paroxysmal form (15[10.6%]), persistent form (43[30.3%]), and permanent form of AF (84[59.1%]). The mean age of these patients was 64.8±10.9 years. AF was verified using ECG Holter monitoring. The control group (n=88) consisted of AH patients without AF with a mean age of 56.5±12.3 years. Echocardiography was carried out according to the recommendations of the American Society of Echocardiography in M- and B-modes. We genotyped SNP rs6817105 (T>C) and examined the relationships among rs6817105 genotype, clinical characteristics, and echocardiographic parameters in AH patients with AF and non-AF AH patients (controls). The rs6817105 minor C allele frequency was significantly higher in AH patients with AF than in non-AF AH patients (71.8% vs. 59.7%, P=0.007). Analysis of the multiplicative model for the rs6817105 SNP showed a significant risk of AF in the carriage of the C allele (OR=1.72, 95% CI: 1.16-2.56, P=0.007). The dominant and additive models for the rs6817105 SNP showed a significant risk of AF with the carriage of the CC+CT genotypes (OR=3.16, 95% CI: 1.37-7.27, P=0.005) and the homozygous CC genotype (OR=1.63, 95% CI: 0.95-2.81, P=0.008), respectively. The allelic distribution showed that the carriage of the C allele was dominant in permanent and persistent AF (110/68.75% vs. 50/31.25% for the T allele [(χ2=22.50, P=0.000], and 73.61% (64/74.41%) vs. 26.39% (22/25.58%) for the T allele [χ2=20.512, P=0.000], respectively). Among AH patients with paroxysmal AF, the C allele prevailed to the greatest extent: 20(90.9%) vs. 2(9.1%) for the T allele (χ2=14.727, P=0.000), indicating a significant accumulation of the C allele and CC genotype among patients with paroxysmal AF. In general, in AH patients with AF, carriers of the CC genotype, the left atrial volume index (LAVI) was significantly higher than the carriers of the CT and TT genotypes: 46.8±13.9 ml/m2 vs. 40.4±13.0 ml/m2 and 36.1±11.0 ml/m2, respectively (P=0.0083). Conclusion: Our results indicate the rs6817105 minor C allele and CC genotype are associated with the risk of developing AF in AH patients of Uzbek nationality. The highest accumulation of the rs6817105 minor C allele and CC genotype is found in paroxysmal AF. In carriers of the rs6817105 CC genotype, the LAVI was significantly larger than in carriers of the CT and TT genotypes.