Association Between Chromosome 4Q25 Polymorphism RS2200733 and the Incidence of Atrial Fibrillation in Bulgarian Patients

Dilyana M. Yakova-Hristova 1 , Martin I. Hristov 1 , Tihomir R. Rashev 2 , Yoana M. Todorova, Pencho T. Tonchev 3 , Nadya Y. Stancheva-Hristova 1  and Snezhanka T. Tisheva-Gospodinova 1
  • 1 Cardiology Division, Bulgaria
  • 2 Division of Molecular Biology, Bulgaria
  • 3 Department of Surgical Propaedeutics, Bulgaria


Atrial fibrillation (AF) is the commonest type of arrhythmia seen in everyday clinical practice, which leads to a significant increase in both morbidity and mortality. Its incidence increases with age and tends to turn into an epidemic. The cause of AF in 10-20% of cases remains unknown. Several mutations and polymorphism that might be responsible for the development of AF have been found, including single nucleotide polymorphisms (SNPs) - rs2200733 and rs10033464 in the long arm of the fourth chromosome. These polymorphisms are selected o the basis of genome- wide association study in Iceland from 2007, the results from which were later confirmed in 4 other large populations. The rs2200733 is a common noncoding polymorphism, described in National Center for Biotechnology Information (NCBI) database dbSNP like NC_000004.12:g.110789013C>T, with a frequency of the less common allele between 0.1 and 0.24. In order to investigate the association between the rs2200733 polymorphism in chromosome 4q25 and the development of AF, we studied the frequency of this polymorphism in patients with heart diseases from the Pleven region, and thus evaluate the relationship between the individual genotype and the clinical condition of the patients. We carried out a case-control study on 80 patients: 40 with AF and 40 without AF- from the Pleven region. None of these had structural heart disease. The study was conducted between November 2015 and November 2017. With deoxyribonucleic acid (DNA) analysis, we determined rs2200733 polymorphism, using a TaqMan-based polymerase chain reaction (PCR). The Cochran-Armitage trend test, the Chi-Squared Pearson correlation, Fisher test we used confirmed the statistically significant association between the rs2200733 polymorphism in chromosome 4q25 and the development of AF. In the population examined, the genotypic frequencies were as follows: CC - 45 (56.2%), CT - 19 (23.8%), TT - 16 (20%), with value of Chi-Square (χ2) 24.496, df=2, p<0.001. Screening for SNPs could be a useful marker for the detection of patients predisposed to AF.

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  • 1. Balabanski TL. [Clinical electrophysiology and treatment of heart arrhythmias]. 2016, 92. Bulgarian.

  • 2. Vulpian A. [Note on the effects of direct faradisation of heart ventricles in dogs]. Arch Physiol Norm Path. 1874;6:975-82. French.

  • 3. Morillo CA, Banerjee A, Perel P, Wood D, Jouven X. Atrial fibrillation: the current epidemic. J Geriatr Cardiol. 2017;14(3):195-203.

  • 4. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, et al.Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Europace. 2010;12:1360-420

  • 5. Husser D, Adams V, Piorkowski C, Hindricks G, Bollmann A. Chromosome 4q25 variants and atrial fibrillation recurrence after catheter ablation. J Am Coll Cardiol. 2010;55(8):747-53.

  • 6. Fatkin D, Otway R, Vandenberg JI. Genes and atrial fibrillation: a new look at an old problem. Circulation. 2007;116:782-92.

  • 7. Judge DP. The complex genetics of atrial fibrillation. J Am Coll Cardiol.. 2012;60(13):1182-4.

  • 8. Kääb S, Darbar D, van Noord C, Dupuis J. Pfeufer A, Newton-Cheh C, et al. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J. 2009;30(7):813-9.

  • 9. Hardy-Weinberg equilibrium calculator including analysis for ascertainment bias. In: OEGE - Online Encyclopedia for Genetic Epidemiology studies [Internet] 2008 [cited 2018 Dec 14]. Available from:

  • 10. Sasieni P. From genotypes to genes: Doubling the sample size. Biometrics. 1997. 3(4):1253-61.

  • 11. Shoemaker MB, Bollmann A, Lubitz S, Ueberham L, Saini H, Montgomery J, et al. Common genetic variants and response to atrial fibrillation ablation. Circ Arrhythm Electrophysiol. 2015;8(2):296-302.

  • 12. Lubitz SA, Ozcan C, Magnani JW, Kaab S, Benjamin EJ, Ellinor P. Genetics of atrial fibrillation: implications for future research directions and personalized medicine. Circ Arrhythm Electrophysiol. 2010;3(3):291-9.


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