Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population.
Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P=0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR=1.32), and genotypic frequencies assuming either an additive or recessive model (OR=1.29, P=0.001 and OR=1.77, P =0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR=1.50, P=0.001 for allelic association; OR=1.45, P=0.001 for an additive model; OR=2.24, P=0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China.
Cong
C
Li
Fan
F
Wang
Yanzong
Y
Yang
Fenfen
F
Fu
Chengqi
C
Xu
Lisong
L
Shi
Sisi
S
Li
Yunlong
Y
Xia
Gang
G
Wu
Xiang
X
Cheng
Hui
H
Liu
Chuchu
C
Wang
Pengyun
P
Wang
Jianjun
J
Hao
Yuhe
Y
Ke
Yuanyuan
Y
Zhao
Mugen
M
Liu
Rongfeng
R
Zhang
Lianjun
L
Gao
Bo
B
Yu
Qiutang
Q
Zeng
Yuhua
Y
Liao
Bo
B
Yang
Xin
X
Tu
Qing K
QK
Wang
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D001281:Atrial Fibrillation / Q000235:genetics*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics; D020521:Stroke / Q000453:epidemiology / Q000235:genetics
D018398:Homeodomain Proteins; C406328:KCNN3 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels; C071660:ZFHX3 protein, human