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Submitted
8 July 2022
Accepted
16 November 2022
Published
5 March 2023
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Abstract

Highlights:



  1. A genetic variable has been identified as an atrial fibrillation risk factor.

  2. Rs2200733 is a type of SNP that increases atrial fibrillation risk, whereas rs3853445, rs6838973, and rs17570669 have the reverse effect.


Abstract:


Atrial fibrillation (AF) is a highly prevalent arrhythmia. The involvement of molecular mechanisms in increased AF risk remains uncertain. However, the paired-like homeodomain transcription factor 2 or pituitary homeobox 2 (PITX2) gene has been linked to AF development. A comprehensive search was carried out to identify all eligible case-control studies in order to assess the association between five single-nucleotide polymorphisms (SNPs) in the PITX2 gene and the risk of AF. This meta-analysis employed the Review Manager (RevMan) software version 5.3 (Cochrane). There were 13 clinical studies, with a total of 11,961 subjects, that met the inclusion criteria. These subjects consisted of 4,440 patients with AF and 7,521 controls. The meta-analysis of five SNP types in the PITX2 gene was done using crude odds ratios (ORs). This revealed that rs2200733 increased the risk of AF (OR=1.80; 95% CI=1.53-2.11; p=0.0005; I2=80%). On the other hand, the other three SNPs decreased the risk of AF, namely, rs385344 (OR=0.75; 95% CI=0.59-0.95; p=0.002; I2=85%), rs6838973 (OR=0.64; 95% CI=0.51-0.81; p=0.0001; I2=73%), and rs17570669 (OR=0.80; 95% CI=0.65-0.98; p=0.03; I2=70%). However, there was no significant association between rs10033464 and AF (OR=1.21; 95% CI=0.97-1.50; p=0.13; I2=83%). In conclusion, depending on the type, SNPs in the PITX2 gene correlate with AF risk factors, either by alleviating or reducing the risk.

Keywords

Atrial fibrillation pituitary homeobox 2 (PITX2) gene chromosome 4q25 single-nucleotide polymorphisms (SNPs) cardiovascular diseases

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How to Cite
Putra, R. M., Dharmadjati, B. B. ., Pikir, B. S. ., Maghfirah , I. ., Isaridha, I. A. ., & Arnindita, J. N. (2023). Five Single-Nucleotide Polymorphisms in the PITX2 Gene as Risk Factors for Atrial Fibrillation. Folia Medica Indonesiana, 59(1), 85–91. https://doi.org/10.20473/fmi.v59i1.37126
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References

  1. Alsagaff MY, Susilo H, Pramudia C, et al (2022). Rapid atrial fibrillation in the emergency department. Heart International 16, 12. doi: 10.17925/hi.2022.16.1.12.
  2. Anter E, Jessup M, Callans DJ (2009). Atrial fibrillation and heart failure. Circulation 119, 2516–25. doi: 10.1161/circulationaha.108. 821306.
  3. Arndt AK, MacRae CA (2014). Genetic testing in cardiovascular diseases. Current Opinion in Cardiolology 29, 235–40. doi: 10.1097/hco. 0000000000000055.
  4. Bai J, Lo A, Gladding PA, et al (2020). In silico investigation of the mechanisms underlying atrial fibrillation due to impaired PITX2. Ed. McCulloch AD. PLOS Computational Biolology 16, e1007678. doi: 10.1371/journal.pcbi.1007678.
  5. Benjamin EJ, Muntner P, Alonso A, et al (2019). Heart disease and stroke statistics”2019 update: A report from the American Heart Association. Circulation. doi: 10.1161/ cir. 0000000000000659.
  6. Bhanushali A, Nair A, Jagdale G, et al (2017). Association of genetic variants at the 4q25 locus with atrial fibrillation in Indian population. Journal of Clinical Laboratory Analysis 31, e22017. doi: 10.1002/jcla.22017.
  7. Chinchilla A, Daimi H, Lozano-Velasco E, et al (2011). PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circulation: Cardiovascular Genetics 4, 269–79. doi: 10.1161/circgenetics. 110.958116.
  8. Franco D, Sedmera D, Lozano-Velasco E (2017). Multiple roles of PITX2 in cardiac development and disease. Journal of Cardiovascular Development and Disease 4, 16. doi: 10.3390/jcdd4040016.
  9. Gudbjartsson DF, Arnar DO, Helgadottir A, et al (2007). Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 448, 353–7. doi: 10.1038/nature06007.
  10. Henningsen KMA, Olesen MS, Pedersen M, et al (2010). Single nucleotide polymorphisms in inflammatory genes and the risk of early onset of lone atrial fibrillation. Inflammation Research 59, 965–9. doi: 10.1007/s00011-010-0210-8.
  11. Hutomo SA, Subagjo A (2020). Difficult atrial fibrilation rate-control and digitalis toxicity in mitral-valve prolapse patient with hyperthyroidism. Cardiovascular and Cardiometabolic Journal 1, 57. doi: 10.20473/ccj. v1i2.2020.57-68.
  12. Kalinderi K, Fragakis N, Koskinas KC, et al (2015). Association between rs2200733 polymorphism on chromosome 4q25 and atrial fibrillation in a Greek population. Hellenic Journal of Cardiology (HJC) 56, 224–9.
  13. Kamel H, Okin PM, Elkind MSV, et al (2016). Atrial fibrillation and mechanisms of stroke. Stroke 47, 895–900. doi: 10.1161/ strokeaha.115.012004.
  14. Kiliszek M, Kozluk E, Franaszczyk M, et al (2016). The 4q25, 1q21, and 16q22 poly-morphisms and recurrence of atrial fibrillation after pulmonary vein isolation. Archives of Medical Science 1, 38–44. doi: 10.5114/aoms. 2015.48284.
  15. Kirchhof P, Kahr PC, Kaese S, et al (2011). PITX2c is expressed in the adult left atrium, and reducing PITX2c expression promotes atrial fibrillation inducibility and complex changes in gene expression. Circulation: Cardiovascular Genetics 4, 123–33. doi: 10.1161/circgenetics.110.958058.
  16. Kolek MJ, Parvez B, Muhammad R, et al (2014). A common variant on chromosome 4q25 is associated with prolonged PR interval in subjects with and without atrial fibrillation. The American Journal of Cardiology 113, 309–13. doi: 10.1016/j.amjcard.2013.08.045.
  17. Kornej J, Börschel CS, Benjamin EJ, et al (2020). Epidemiology of atrial fibrillation in the 21st Century. Circulation Research 127, 4–20. doi: 10.1161/circresaha.120.316340.
  18. Lee KT, Yeh HY, Tung CP, et al (2010). Association of RS2200733 but not RS10033464 on 4q25 with atrial fibrillation based on the recessive model in a Taiwanese population. Cardiology 116, 151–6. doi: 10.1159/000318172.
  19. Lemmens R, Buysschaert I, Geelen V, et al (2010). The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke 41, 1850–7. doi: 10.1161/strokeaha.110. 587980.
  20. Lo CK, Mertz D, Loeb M, et al (2014). Newcastle-Ottawa Scale: Comparing reviewers' to authors' assessments. BMC Medical Research Methodology 14. doi: 10.1186/1471-2288-14-45.
  21. Lubitz SA, Yin X, Fontes JD, et al (2010). Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 304, 2263. doi: 10.1001/jama.2010.1690.
  22. Maesen B, Van-Loo I, Pison L, et al (2016). Surgical ablation of atrial fibrillation: Is electrical isolation of the pulmonary veins a must? Journal of Atrial Fibrillation 9, 1426. doi: 10.4022/jafib.1426.
  23. Mohanty S, Santangeli P, Bai R, et al (2013). Variant rs2200733 on chromosome 4q25 confers increased risk of atrial fibrillation: Evidence from a meta- analysis. Journal of Cardiovascular Electrophysio-logy 24, 155–61. doi: 10.1111/jce.12017.
  24. Morillo CA, Banerjee A, Perel P, et al (2017). Atrial fibrillation: The current epidemic. Journal of Geriatric Cardiology 14, 195–203. doi: 10.11909/j.issn.1671-5411.2017.03.011.
  25. Olesen MS, Holst AG, Jabbari J, et al (2012). Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years. Canadian Journal of Cardiology 28, 191–5. doi: 10.1016/j.cjca.2011.11.016.
  26. Purwowiyoto SL, Surya SP (2021). A case of malignant right coronary artery: Frequent angina in young person. Folia Medica Indonesiana 57, 341. doi: 10.20473/fmi.v57i4.19233.
  27. Schnabel RB, Kerr KF, Lubitz SA, et al (2011). Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation. Circulation: Cardiovascular Genetics 4, 557–64. doi: 10.1161/circgenetics.110.959197.
  28. Smith JG, Almgren P, Engström G, et al (2012). Genetic polymorphisms for estimating risk of atrial fibrillation: A literature-based meta-analysis. Journal of Internal Medicine 272, 573–82. doi: 10.1111/j.1365-2796.2012.02563.x.
  29. Staerk L, Sherer JA, Ko D, et al (2017). Atrial fibrillation. Circulation Research 120, 1501–17. doi: 10.1161/circresaha.117.309732.
  30. Stavrakis S, Nakagawa H, Po SS, et al (2015). The role of the autonomic ganglia in atrial fibrillation. JACC Clinical Electrophysiology 1, 1–13. doi: 10.1016/j.jacep.2015.01.005.
  31. Sulistyorini N, Yudianto A, Margaret N (2017). Nucleotide variance of mitochondrial DNA D-Loop 126 bp (nt: 34-159) region in Madurese. Folia Medica Indonesiana 52, 80. doi: 10.20473/fmi.v52i2.5215.
  32. Yazid M, Rahman MA (2020). Variable step dynamic threshold local binary pattern for classification of atrial fibrillation. Artificial Intelligence in Medicine 108, 101932. doi: 10.1016/j.artmed.2020.101932.
  33. Yuan F, Zhao L, Wang J, et al (2013). PITX2c loss-of-function mutations responsible for congenital atrial septal defects. International Journal of Medical Science 10, 1422–9. doi: 10.7150/ ijms.6809.
  34. Yudianto A, Sosiawan A, Margaret N (2017). CODISSTRLoci (CSF1PO, THOI, TPOX, vWA) genetic variation analysis in Madurese. Folia Medica Indonesiana 52, 1. doi: 10.20473/fmi. v52i1.5196.
  35. Zhao CM, Peng LY, Li L, et al (2015). PITX2 loss- of-function mutation contributes to congenital endocardial cushion defect and Axenfeld-Rieger syndrome ed. Ramchandran R. PLoS One 10, e0124409. doi: 10.1371/journal.pone.0124409.
  36. Zhao L, Zhang G, Wen Z, et al (2017). Common variants predict recurrence after nonfamilial atrial fibrillation ablation in Chinese Han population. International Journal of Cardiology 227, 360–6. doi: 10.1016/j.ijcard.2016.11.057.