Comprehensive mutation scanning of KCNQ1 in 111 Han Chinese patients with lone atrial fibrillation.
OBJECTIVE
To determine the extent to which genetic variation in the potassium channel gene KCNQ1 causes atrial fibrillation (AF).


METHODS
Case-control study.


METHODS
National University Hospital, Singapore.


METHODS
Han Chinese patients (n=111) with lone AF (onset <60 years and lacking risk factors) and 265 Han Chinese controls.


METHODS
Blood draw, 12-lead electrocardiogram and transthoracic echocardiogram were performed on patients with AF at enrolment.


METHODS
DNA sequence variants in the coding region and exon-intron boundaries of KCNQ1 as detected by direct sequencing.


RESULTS
Four previously reported coding variants were identified: I145I, S546S, P448R and G643S. An additional 19 non-coding variants were identified, nine of which are newly reported. None were predicted to create a cryptic splicing site. The allele frequencies of the two non-synonymous variants did not differ significantly in the AF cases compared with 265 Han Chinese controls (P448R: 10.8% in cases vs 8.6% in controls, p=0.41; G643S: 1.4% in cases vs 0.8% in controls, p=0.43).


CONCLUSIONS
Comprehensive mutation scanning of KCNQ1 did not identify novel pathogenic mutations or risk-conferring polymorphisms. As in Caucasians, genetic variation in KCNQ1 is not a common cause of AF in Han Chinese. Routine genetic testing of KCNQ1 for AF is, therefore, not warranted.
The Department of Medicine, Cardiovascular Division (Cardiac Arrhythmia Centre), University of Minnesota, Minneapolis, Minnesota, USA; Department of Medicine, Cardiovascular Division, National University of Singapore, Singapore.
Lin Y
LY
Chen
Department of Paediatrics, National University of Singapore, Singapore.
June M
JM
Goh
Cardiac Department, National University Hospital, Singapore.
Raymond C
RC
Wong
Department of Cardiology, National Heart Centre, Singapore.
Li-Fern
LF
Hsu
Department of Cardiology, Tan Tock Seng Hospital, Singapore.
David
D
Foo
The Department of Medicine, Cardiovascular Division (Cardiac Arrhythmia Centre), University of Minnesota, Minneapolis, Minnesota, USA.
David G
DG
Benditt
Department of Medicine, Cardiovascular Division, National University of Singapore, Singapore.
Lieng H
LH
Ling
Department of Paediatrics, National University of Singapore, Singapore.
Chew K
CK
Heng
Atrial fibrillation; KCNQ1; genetics; potassium channel