Table 1

Atrial fibrillation (AF) susceptibility genes and loci

AF susceptibility genes

AF susceptibility loci


Gene

Mechanism

Ref.

Chromosomal locus

Candidate gene

Ref.


Potassium channel

Large-scale candidate gene or genome-wide association study

KCNQ1

Enhanced repolarization (increased IKs)

[61-65]

1q21

IL6R

[66]

KCNE1

Enhanced repolarization (increased IKs)

[9,67-69]

1q21

KCNN3

[15,16]

KCNE2

Enhanced repolarization (increased IKs)

[70]

1q24

PRRX1

[16]

KCNE5

Enhanced repolarization (increased IKs)

[71]

4q25

PITX2

[12-16]

KCNH2

Enhanced repolarization (increased IKr)

[72,73]

7q31

CAV1

[16]

KCNJ2

Enhanced repolarization (increased IK1)

[74]

9q22

C9orf3

[16]

KCNA5

Delayed repolarization and afterdepolarizations (decreased IKur)

[75]

10q22

SYNPO2L/MYOZ1

[16]

Sodium channel

14q23

SYNE2

[16]

SCN5A

Hyperpolarizing shift in inactivation (loss-of-function)/depolarizing shift in inactivation (gain-of-function)

[76-81]

15q24

HCN4

[16]

SCN1B

Decreased INa current and altered channel gating

[82]

16q22

ZFHX3

[16]

SCN2B

Decreased INa current and altered channel gating

[82]

Familial loci without known gene

Ion channel-related

6q14-q16

-

[83]

GJA5

Impaired cellular transport and intercellular electrical coupling, increased dispersion of refractoriness

[84-87]

10p11-q21

-

[88]

ANK2

Loss-of-function reduces expression and membrane targeting of Cav1.3 (decreased ICa,L)

[89,90]

10q22-q24

-

[91]

Non-ion channel

LMNA

Disruption of nuclear function or altered interaction with cytoplasmic proteins

[92-95]

NUP155

Reduced nuclear membrane permeability, enhanced repolarization

[96,97]

AGT

Unknown

[98,99]

ACE

Insertion/deletion, unknown mechanism

[100-102]

NPPA

Mutant peptide, enhanced repolarization

[103]


AF susceptibility genes were based on prior linkage mapping or candidate gene sequencing efforts. AF susceptibility loci were based on candidate gene chip or genome-wide association studies.

Lubitz and Ellinor BMC Medicine 2012 10:155   doi:10.1186/1741-7015-10-155

Open Data