PITX2-dependent gene regulation in atrial fibrillation and rhythm control

doi:10.1113/JP273123

Review

. 2017 Jun 15;595(12):4019-4026.

doi: 10.1113/JP273123. Epub 2017 Apr 25.

PITX2-dependent gene regulation in atrial fibrillation and rhythm control

Fahima Syeda¹, Paulus Kirchhof^{1

2

3}, Larissa Fabritz^{1

2

4}

Affiliations

¹ Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
² Department of Cardiology, UHB NHS Trust, Birmingham, UK.
³ Department of Cardiology, SWBT, Birmingham, UK.
⁴ Department of Cardiovascular Medicine, Division of Rhythmology, University Hospital Münster, Münster, Germany.

PMID: 28217939
PMCID: PMC5471504
DOI: 10.1113/JP273123

Review

PITX2-dependent gene regulation in atrial fibrillation and rhythm control

Fahima Syeda et al. J Physiol. 2017.

. 2017 Jun 15;595(12):4019-4026.

doi: 10.1113/JP273123. Epub 2017 Apr 25.

Authors

Fahima Syeda¹, Paulus Kirchhof^{1

2

3}, Larissa Fabritz^{1

2

4}

Affiliations

¹ Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
² Department of Cardiology, UHB NHS Trust, Birmingham, UK.
³ Department of Cardiology, SWBT, Birmingham, UK.
⁴ Department of Cardiovascular Medicine, Division of Rhythmology, University Hospital Münster, Münster, Germany.

PMID: 28217939
PMCID: PMC5471504
DOI: 10.1113/JP273123

Abstract

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. There are several major mechanisms that cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription factor PITX2. The effect of these common gene variants on cardiac PITX2 mRNA is currently under study. PITX2 protein regulates right-left differentiation of the embryonic heart, thorax and aorta. PITX2 is expressed in the adult left atrium, but much less so in other heart chambers. Pitx2 deficiency results in electrical and structural remodelling, and impaired repair of the heart in murine models, all of which may influence AF through divergent mechanisms. PITX2 levels and single nucleotide polymorphisms on chromosome 4q25 may also be a predictor of the effectiveness of anti-arrhythmic drug therapy.

Keywords: Pitx2; antiarrhythmic drugs; atrial fibrillation; gene regulation; mouse model; transcription factors.

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References

1. Aguirre LA, Alonso ME, Badia‐Careaga C, Rollan I, Arias C, Fernandez‐Minan A, Lopez‐Jimenez E, Aranega A, Gomez‐Skarmeta JL, Franco D & Manzanares M (2015). Long‐range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP . BMC Biol 13, 26. - PMC - PubMed
1. Bassand JP, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KA, Goldhaber SZ, Goto S, Haas S, Hacke W, Kayani G, Mantovani LG, Misselwitz F, Ten Cate H, Turpie AG, Verheugt FW & Kakkar AK; GARFIELD‐AF Investigators (2016). Two‐year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD‐AF. Eur Heart J 37, 2882–2889. - PMC - PubMed
1. Beermann J, Piccoli MT, Viereck J & Thum T (2016). Non‐coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96, 1297–1325. - PubMed
1. Benjamin EJ, Rice KM, Arking DE, Pfeufer A, van Noord C, Smith AV, Schnabel RB, Bis JC, Boerwinkle E, Sinner MF, Dehghan A, Lubitz SA, D'Agostino RB Sr, Lumley T, Ehret GB, Heeringa J, Aspelund T, Newton‐Cheh C, Larson MG, Marciante KD, Soliman EZ, Rivadeneira F, Wang TJ, Eiriksdottir G, Levy D, Psaty BM, Li M, Chamberlain AM, Hofman A, Vasan RS, Harris TB, Rotter JI, Kao WH, Agarwal SK, Stricker BH, Wang K, Launer LJ, Smith NL, Chakravarti A, Uitterlinden AG, Wolf PA, Sotoodehnia N, Kottgen A, van Duijn CM, Meitinger T, Mueller M, Perz S, Steinbeck G, Wichmann HE, Lunetta KL, Heckbert SR, Gudnason V, Alonso A, Kaab S, Ellinor PT & Witteman JC (2009). Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 41, 879–881. - PMC - PubMed
1. Campione M, Ros MA, Icardo JM, Piedra E, Christoffels VM, Schweickert A, Blum M, Franco D & Moorman AF (2001). Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice. Dev Biol 231, 252–264. - PubMed

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[1] Aguirre LA, Alonso ME, Badia‐Careaga C, Rollan I, Arias C, Fernandez‐Minan A, Lopez‐Jimenez E, Aranega A, Gomez‐Skarmeta JL, Franco D & Manzanares M (2015). Long‐range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP . BMC Biol 13, 26. - PMC - PubMed

[2] Aguirre LA, Alonso ME, Badia‐Careaga C, Rollan I, Arias C, Fernandez‐Minan A, Lopez‐Jimenez E, Aranega A, Gomez‐Skarmeta JL, Franco D & Manzanares M (2015). Long‐range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP . BMC Biol 13, 26. - PMC - PubMed

[3] Bassand JP, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KA, Goldhaber SZ, Goto S, Haas S, Hacke W, Kayani G, Mantovani LG, Misselwitz F, Ten Cate H, Turpie AG, Verheugt FW & Kakkar AK; GARFIELD‐AF Investigators (2016). Two‐year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD‐AF. Eur Heart J 37, 2882–2889. - PMC - PubMed

[4] Bassand JP, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KA, Goldhaber SZ, Goto S, Haas S, Hacke W, Kayani G, Mantovani LG, Misselwitz F, Ten Cate H, Turpie AG, Verheugt FW & Kakkar AK; GARFIELD‐AF Investigators (2016). Two‐year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD‐AF. Eur Heart J 37, 2882–2889. - PMC - PubMed

[5] Beermann J, Piccoli MT, Viereck J & Thum T (2016). Non‐coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96, 1297–1325. - PubMed

[6] Beermann J, Piccoli MT, Viereck J & Thum T (2016). Non‐coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96, 1297–1325. - PubMed

[7] Benjamin EJ, Rice KM, Arking DE, Pfeufer A, van Noord C, Smith AV, Schnabel RB, Bis JC, Boerwinkle E, Sinner MF, Dehghan A, Lubitz SA, D'Agostino RB Sr, Lumley T, Ehret GB, Heeringa J, Aspelund T, Newton‐Cheh C, Larson MG, Marciante KD, Soliman EZ, Rivadeneira F, Wang TJ, Eiriksdottir G, Levy D, Psaty BM, Li M, Chamberlain AM, Hofman A, Vasan RS, Harris TB, Rotter JI, Kao WH, Agarwal SK, Stricker BH, Wang K, Launer LJ, Smith NL, Chakravarti A, Uitterlinden AG, Wolf PA, Sotoodehnia N, Kottgen A, van Duijn CM, Meitinger T, Mueller M, Perz S, Steinbeck G, Wichmann HE, Lunetta KL, Heckbert SR, Gudnason V, Alonso A, Kaab S, Ellinor PT & Witteman JC (2009). Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 41, 879–881. - PMC - PubMed

[8] Benjamin EJ, Rice KM, Arking DE, Pfeufer A, van Noord C, Smith AV, Schnabel RB, Bis JC, Boerwinkle E, Sinner MF, Dehghan A, Lubitz SA, D'Agostino RB Sr, Lumley T, Ehret GB, Heeringa J, Aspelund T, Newton‐Cheh C, Larson MG, Marciante KD, Soliman EZ, Rivadeneira F, Wang TJ, Eiriksdottir G, Levy D, Psaty BM, Li M, Chamberlain AM, Hofman A, Vasan RS, Harris TB, Rotter JI, Kao WH, Agarwal SK, Stricker BH, Wang K, Launer LJ, Smith NL, Chakravarti A, Uitterlinden AG, Wolf PA, Sotoodehnia N, Kottgen A, van Duijn CM, Meitinger T, Mueller M, Perz S, Steinbeck G, Wichmann HE, Lunetta KL, Heckbert SR, Gudnason V, Alonso A, Kaab S, Ellinor PT & Witteman JC (2009). Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet 41, 879–881. - PMC - PubMed

[9] Campione M, Ros MA, Icardo JM, Piedra E, Christoffels VM, Schweickert A, Blum M, Franco D & Moorman AF (2001). Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice. Dev Biol 231, 252–264. - PubMed

[10] Campione M, Ros MA, Icardo JM, Piedra E, Christoffels VM, Schweickert A, Blum M, Franco D & Moorman AF (2001). Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice. Dev Biol 231, 252–264. - PubMed

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PITX2-dependent gene regulation in atrial fibrillation and rhythm control

Affiliations

PITX2-dependent gene regulation in atrial fibrillation and rhythm control

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Abstract

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