Table 1

Some recent breakthroughs in atrial fibrillation genetics

Gene or locus

Mechanism

Methods

References

4q25 (PITX2)

Protein is involved in embryogenic cardiomyocyte development

Genome-wide association

[51,52]

6q14-16

Unknown

Linkage

[31]

10q22-24

Unknown

Linkage

[16]

ACE

Mutation induces atrial fibrosis, resulting in conduction heterogeneity

Candidate gene

[44]

ANP

A frameshift mutation shortens APD

Candidate gene

[45]

Connexin 40 (GJA5)

Mutation of a gap-junction protein impairs electrical coupling, resulting in atrial conduction heterogeneity

Candidate gene

[41]

KCNE2

A gain-of-function mutation increases K⁺ current density, leading to shortening of APD and thus increasing reentry

Linkage

[35]

KCNH2

A gain-of-function mutation increases K⁺ current density, leading to shortening of APD and thus increasing reentry

Linkage

[32]

KCNJ2

A gain-of-function mutation increases K⁺ current density, leading to shortening of APD and thus increasing reentry

Linkage

[19]

KCNQ1

A gain-of-function mutation increases K⁺ current density, leading to shortening of APD and thus increasing reentry

Linkage

[18]

NPC

Mutation of a nuclear envelope protein affects transcription of vital proteins

Linkage and fine mapping

[40]

SCN5A

A mutation in a Na⁺ channel gene gives decreased sodium current and shorter wavelength and thus more stable AF

Candidate gene

[39]

Abbreviations: ACE, angiotensin converting enzyme; AF, atrial fibrillation; ANP, atrial natriuretic peptide; APD, action potential duration; NPC, nuclear pore complex.

Damani and Topol Genome Medicine 2009 1:54   doi:10.1186/gm54