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Related Experiment Videos

Cx40 polymorphism in human atrial fibrillation.

Richard N W Hauer1, W Antoinette Groenewegen, Mehran Firouzi

  • 1University Medical Center, Utrecht, The Netherlands.

Advances in Cardiology
|May 2, 2006
PubMed
Summary

Rare connexin40 (Cx40) gene polymorphisms are linked to an increased coefficient of dispersion (CD), creating a substrate for atrial fibrillation (AF) reentry. This finding may explain AF predisposition in individuals with these genetic variations.

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Area of Science:

  • Cardiology
  • Genetics
  • Electrophysiology

Background:

  • Connexin40 (Cx40) gene polymorphisms (-44 G>A and +71 A>G) are found in ~7% of the population.
  • Cx40 is crucial in atrial electrophysiology; its polymorphisms, particularly in homozygosity with SCN5A mutations, are linked to familial atrial standstill.
  • Spatial dispersion of refractoriness, measured by the coefficient of dispersion (CD), promotes atrial fibrillation (AF) reentry.

Purpose of the Study:

  • To investigate the association between Cx40 gene polymorphisms and the atrial electrophysiologic substrate favoring AF.
  • To determine if these polymorphisms influence the coefficient of dispersion (CD), a marker for reentry.

Main Methods:

  • Calculated CD from local mean fibrillatory intervals during induced AF in 30 patients.

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  • Assessed CD in patients with and without AF, considering CD <= 3.0 as normal.
  • Determined Cx40 genotypes using DNA sequencing.

    • Main Results:

    • Mean CD was significantly higher in AF patients (5.96 +/- 0.70) compared to non-AF patients (1.59 +/- 0.18).
    • Thirteen of fourteen AF patients exhibited enhanced CD (>3.0).
    • Carriers of the -44 AA genotype showed significantly higher CD (6.37 +/- 1.21) than -44 GG genotype carriers (2.38 +/- 0.39).

    Conclusions:

    • The studied Cx40 gene polymorphisms are associated with enhanced CD.
    • This enhanced CD represents a substrate for reentry, contributing to the initiation of atrial fibrillation (AF).