Association between single nucleotide polymorphisms rs2200733 and rs10033464 at chromosome 4q25 and thyrotoxic atrial fibrillation

Abstract

Background. Thyrotoxic atrial fibrillation (TAF) genesis does not exclude a genetic component due to the difference in thyroid hormones effects on the cardiovascular system in similar patients. According to genomewide association studies (GWAS), the first locus associated with non-thyrotoxic atrial fibrillation (AF) was locus 4q25, and the first single-nucleotide polymorphisms in it identified as risk factors for AF were polymorphisms rs2200733 and rs10033464. Their connection with TAF remains unclear.Objective. To investigate the possible association of the two single nucleotide polymorphisms rs2200733 and rs10033464 with TAF.Design and methods. The association of TAF and other thyrotoxic cardiomyopathy manifestations with the studied polymorphisms was examined in a sample of 150 patients with Graves’ disease and overt thyrotoxicosis, 18.7 % of whom had TAF. Genotyping was preformed using real time PCR.Results. A significant predominance of TT genotype for both polymorphisms was revealed: p=0.038 for rs10033464, p<0.001 for rs2200733. TT genotype frequency in TAF patients compared with non-TAF participants: 7.4 % vs 1.6 % for rs10033464, 17.9 % vs 0.8 % for rs2200733. When assessing the frequency of genotypes depending on the presence of other thyrotoxic cardiomyopathy manifestations, TT genotype was more common in patients with ventricular premature beats, p=0.001.Conclusion. TT genotype of rs2200733 and rs10033464 polymorphisms at 4q25 locus is associated with a higher incidence of TAF and ventricular extrasystole in thyrotoxic patients.