Function follows form: Cardiac conduction system defects in <i>Nkx2‐5</i> mutation

Jay, Patrick Y.; Harris, Brett S.; Buerger, Antje; Rozhitskaya, Olga; Maguire, Colin T.; Barbosky, Laura A.; McCusty, Ellen; Berul, Charles I.; O’Brien, Terrence X.; Gourdie, Robert G.; Izumo, Seigo

doi:10.1002/ar.a.20102

Cited by 29 publications

(19 citation statements)

References 42 publications

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“…Another study (6) has reported interstrain differences in the QRS complex duration. Studies (23,30) have suggested that the distribution pattern of the Purkinje fiber network in the myocardium and ventricular wall thickness play an important role in ventricle excitation time. Interstrain differences in the QRS complex duration may reflect interstrain differences in ventricular wall thickness.…”

Section: Discussionmentioning

confidence: 99%

Genetic influence on electrocardiogram time intervals and heart rate in aging mice

Shu-qin¹,

Tsaih²,

Yuan³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Understanding the genetic influence on ECG time intervals and heart rate (HR) is important for identifying the genes underlying susceptibility to cardiac arrhythmias. The objective of this study was to determine the genetic influence on ECG parameters and their age-related changes in mice. ECGs were recorded in lead I on 8 males and 8 females from each of 28 inbred strains at the ages of 6, 12, and 18 mo. Significant interstrain differences in the P-R interval, QRS complex duration, and HR were found. Age-related changes in the P-R interval, QRS complex duration, and HR differed among strains. The P-R interval increased with age in 129S1/SvlmJ females. The QRS complex duration decreased with age in C57BR/J males and DBA2/J females but increased in NON/ShiLtJ females. HR decreased in C57L/J females and SM/J and P/J males but increased in BALB/cByJ males. Differences between males and females were found for HR in SJL/J mice and in the P-R interval in 129S1/SvlmJ mice. Broad-sense heritability estimates of ECG time intervals and HR ranged from 0.31 for the QRS complex duration to 0.52 for the P-R interval. Heritability estimates decreased with age for the P-R interval. Our study revealed that genetic factors play a significant role on cardiac conduction activity and age-related changes in ECG time intervals and HR.

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Section: Discussionmentioning

confidence: 99%

Genetic influence on electrocardiogram time intervals and heart rate in aging mice

Shu-qin¹,

Tsaih²,

Yuan³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…NKX2-5 (rs251253 P = 9.5×10 -13 ) is the homolog of the Drosophila tinman gene and encodes the cardiac specific homeobox transcription factor Nkx2.5 (Csx). Mutations can cause atrium septum defect (ASD) with conduction defects (OMIM #108900), tetralogy of Fallot (OMIM #187500), and high degree AV block (31). In the NKX2-5 gene region the association extends over 200Kb and includes three other genes BNIP1 , C5orf41 , and ATP6V0E1 .…”

mentioning

confidence: 99%

Genome-wide association study of PR interval

et al. 2010

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The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation (AF). To identify underlying common genetic variation, we meta-analyzed genome-wide association results for PR interval from seven community-based studies of European-ancestry individuals in the CHARGE consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N=28,517). Statistically significant loci (P<5×10-8) were tested for association with AF (N=5,741 cases). We identified nine loci associated with PR interval. At chromosome 3p22.2, we observed two independent associations in voltage gated sodium channel genes SCN10A and SCN5A, while six loci were near cardiac developmental genes CAV1/CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5/TBX3. Another signal was at ARHGAP24, a locus without known relevance to the heart. Five of the nine loci, SCN5A, SCN10A, NKX2-5, CAV1/CAV2, and SOX5, were also associated with AF (P<0.0056). Common genetic variation, particularly in ion channel and developmental genes, contributes significantly to atrial and atrioventricular conduction and to AF risk.

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“…The atrioventricular node was first described in 1906 by Sunao Tawara working in Ludwig Aschoff's laboratory in Germany (Boyett, 2009). Recent genetic work in animals and human beings suggest that mutations in the transcription factor Nkx2.5 may be associated with conduction system developmental abnormalities (Gittenberger-De Groot et al, 2007;Jay et al, 2004). The atrial and ventricular working myocardial cells are similar in characteristics but different in anatomic arrangement (Boyett, 2009;Gourdie et al, 2003;Ho & Anderson, 1990).…”

Section: Atrial Embryologymentioning

confidence: 99%