Assessment of Association of rs2200733 SNP on Chromosome 4q25 with the Risk of the Development of Atrial Fibrillation in the Russian Population

ORIGINAL ARTICLE
Vladimir A. Shulman, Natalya V. Aksyutina, Elena A. Aldanova, Svetlana Yu. Nikulina, Vasily V. Kozlov, Larissa G. Soinova, Oksana A. Gavrilyuk

 
International Journal of Biomedicine. 2018;8(4):280-283.   
DOI: 10.21103/Article8(4)_OA1
Originally published December 15, 2018  

Abstract: 

The aim of our case-control study was to investigate the possible genetic association of the rs2200733 SNP on chromosome 4q25 with AF in the Russian population as this association has not been examined before in this ethnicity.
Methods and Results: A total of 76 unrelated individuals diagnosed with AF and 73 control subjects without any cardiovascular pathology were included in this study. The diagnosis of AF was based on ECG and/or Holter ECG data following standard diagnostic criteria. We found that the TT genotype of the rs2200733 SNP was associated with a higher risk of AF (OR=1.4, 95% CI: 1.1-12.4). The homozygote minor rare allele genotype TT of the rs2200733 SNP tended to elevate the risk of lone AF development (OR=2.5, 95% CI: 1.2-19.5). A risk of secondary AF development did not depend on rs2200733 SNP on chromosome 4q25 (OR=0.5, 95% CI: 0.2-1.3).
Conclusion: Our results provide additional evidence for the association between the rs2200733 (4q25)  SNP on chromosome 4q25 and AF, emphasizing the need for further studies examining the role of this polymorphism in AF.

Keywords: 
atrial fibrillation • single nucleotide polymorphism • chromosome 4q25 • rs2200733 • odds ratio
References: 
  1. Nikulina SY, Schulman VA, Kuznetsova OO, Aksjutina NV,  Shesternja PA, Chernova AA, et al. Clinical and genetic pecularities of atrial fibrillation. Rational Pharmacotherapy in Cardiology .2008;4(2):13-8. [Article in Russian].
  2. Nikulina SY, Schulman VA, Kuznetsova OO, Aksjutina NV, Chernova AA, et al. Atrial fibrillation: the genealogy and genetics. Siberian Medical Review'. 2008;52(4):4–10. [Article in Russian].
  3. Tsai CT, Lai LP, Hwang JJ, Lin JL, Chiang FT. Molecular genetics of atrial fibrillation. J Am Coll Cardiol. 2008;52(4):241-50. doi: 10.1016/j.jacc.2008.02.072. PubMed
  4. Judge DP. The complex genetics of atrial fibrillation. J Am Coll Cardiol. 2012;60(13):1182-4. doi: 10.1016/j.jacc.2012.04.031.PubMed
  5. Ellinor PT, Yi BA, MacRae CA. Genetics of atrial fibrillation. Med Clin North Am. 2008;92(1):41-51, x. PubMed
  6. Olesen MS, Holst AG, Jabbari J, Nielsen JB, Christophersen IE, Sajadieh A, et al. Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years. Can J Cardiol.2012;28(2):191-5. doi: 10.1016/j.cjca.2011.11.016. PubMed
  7. Kiliszek M, Franaszczyk M, Kozluk E, Lodzinski P, Piatkowska A, Broda G, et al. Association between variants on chromosome 4q25, 16q22 and 1q21 and atrial fibrillation in the Polish population. PLoS One. 2011;6(7):e21790. doi: 10.1371/journal.pone.0021790. PubMed
  8. Diagnosis and treatment of atrial fibrillation. Recommendation of RCS, ASSC and ACS. Russian J Cardiol. 2013;4s(3).
  9. Lloyd-Jones ДМ, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042-6. PubMed
  10. Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448(7151):353-7. PubMed
  11. Ferran A, Alegret JM, Subirana I, Aragonès G, Lluis-Ganella C, Romero-Menor C, et al. Association between rs2200733 and rs7193343 genetic variants and atrial fibrillation in a Spanish population, and meta-analysis of previous studies. Rev Esp Cardiol (Engl Ed). 2014;67(10):822-9. doi: 10.1016/j.rec.2013.12.019. PubMed
  12. Mohanty S, Santangeli P, Bai R, Di Biase L, Mohanty P, Pump A, Natale A. Variant rs2200733 on chromosome 4q25 confers increased risk of atrial fibrillation: evidence from a meta-analysis. J Cardiovasc Electrophysiol.2013;24(2):155-61. doi: 10.1111/jce.12017. PubMed
  13. Goodloe AH, Herron KJ, Olson TM. Uncovering an intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation. Am J Cardiol.2011;107(12):1802-5. doi: 10.1016 /j.amjcard.2011.02.326. PubMed
  14. Lubitz SA, Sinner MF, Lunetta KL, Makino S, Pfeufer A, Rahman R, et al. Independent susceptibility markers for atrial fibrillation on chromosome 4q25. Circulation. 2010;122(10):976-84. doi:10.1161/CIRCULATIONAHA.109.886440. PubMed
  15. Viviani Anselmi C, Novelli V, Roncarati R, Malovini A, Bellazzi R, Bronzini R, et al. Association of rs2200733 at 4q25 with atrial flutter/fibrillation diseases in an Italian population. Heart. 2008;94(11):1394-6. doi: 10.1136/hrt.2008.148544. PubMed
  16. Lee KT, Yeh HY, Tung CP, Chu CS, Cheng KH, Tsai WC, et al. Association of RS2200733 but not RS10033464 on 4q25 with atrial fibrillation based on the recessive model in a Taiwanese population. Cardiology. 2010;116(3):151-6. doi: 10.1159/000318172. PubMed
  17. Kalinderi K, Fragakis N, Koskinas KC, Katritsis D, Letsas K, Efremidis M, et al. Association Between rs2200733 Polymorphism on Chromosome 4q25 and Atrial Fibrillation in a Greek Population. Hellenic J Cardiol. 2015;56(3):224-9. PubMed
  18. Shi L, Li C, Wang C, Xia Y, Wu G, Wang F, et al. Assessment of association of rs2200733 on chromosome 4q25 with atrial fibrillation and ischemic stroke in a Chinese Han population. Hum Genet. 2009;126(6):843-9. doi: 10.1007/s00439-009-0737-3. PubMed
  19. Kolek MJ, Parvez B, Muhammad R, Shoemaker MB, Blair MA, Stubblefield T, et al. A common variant on chromosome 4q25 is associated with prolonged PR interval in subjects with and without atrial fibrillation. Am J Cardiol. 2014;113(2):309-13. doi: 10.1016/j.amjcard.2013.08.045. PubMed
  20. Kahr PC, Piccini I, Fabritz L, Greber B, Schöler H, Scheld HH, et al. Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue. PLoS One. 2011;6(10):e26389. doi: 10.1371/journal.pone.0026389. PubMed
  21. Kirchhof P, Kahr PC, Kaese S, Piccini I, Vokshi I, Scheld HH, et al.  PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression. Circ Cardiovasc Genet. 2011 Apr;4(2):123-33. doi: 10.1161/CIRCGENETICS.110.958058. PubMed
  22. Wang J, Klysik E, Sood S, Johnson RL, Wehrens XH, Martin JF. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9753-8. doi: 10.1073/pnas.0912585107. PubMed
  23. Henningsen KM, Olesen MS, Haunsoe S, Svendsen JH. Association of rs2200733 at 4q25 with early onset of lone atrial fibrillation in young patients. Scand Cardiovasc J. 2011;45(6):324-6. doi: 10.3109/14017431.2011.594081. PubMed
  24. Roberts JD, Hsu JC, Aouizerat BE, Pullinger CR, Malloy MJ, Kane JP, et al. Impact of a 4q25 genetic variant in atrial flutter and on the risk of atrial fibrillation after cavotricuspid isthmus ablation. J Cardiovasc Electrophysiol. 2014;25(3):271-7. doi: 10.1111/jce.12317. PubMed
  25. Bhanushali A, Nair A, Jagdale G, Suvarna T, Das BR. Association of Genetic Variants at the 4q25 Locus with Atrial Fibrillation in Indian Population. J Clin Lab Anal. 2017 Jan;31(1). doi: 10.1002/jcla.22017. PubMed
  26. Chen F, Yang Y, Zhang R, Zhang S, Dong Y, Yin X, et al. Polymorphism rs2200733 at chromosome 4q25 is associated with atrial fibrillation recurrence after radiofrequency catheter ablation in the Chinese Han population. Am J Transl Res. 2016;8(2):688-97. PubMed

Download Article
Received October 26, 2018.
Accepted November 12, 2018.
©2018 International Medical Research and Development Corporation.