Genetic polymorphism of KCNH2 confers predisposition of acquired atrial fibrillation in Chinese.
BACKGROUND
Nonfamiliar atrial fibrillation (AF) is usually associated with acquired structural heart disease, including valvular heart disease, coronary artery disease, and hypertension. Suggestive evidence indicates that these forms of acquired AF are more likely to occur in individuals with a genetic predisposition. We investigated the effect of the potassium channel voltage-gated subfamily member 2 (KCNH2) gene on the prevalence of acquired AF in a Chinese population.


METHODS
In a pair-matched, hospital-based case control study (297 vs 297) conducted in Chinese Hans, we investigated 4 tagging single nucleotide polymorphisms (tSNPs), rs1805120, rs1036145, rs3807375, and rs2968857 in the KCNH2 gene, and determined their association with AF acquired from structural heart diseases.


RESULTS
We did not observe the association of rs1036145, rs3807375, and rs2968857 with AF. However, we determined that the tSNP, rs1805120, in exon 6 confers the risk of AF in Chinese Hans. Both genotype and allele frequencies of rs1805120 were distributed differently in cases and controls (P = 0.0289 and P = 0.0172, respectively). The most significant association was observed under a recessive model for the minor GG genotype with a 1.45-fold risk of developing AF (95% confidence interval 1.09-1.93, P = 0.012). The significance remained after controlling for the covariates of age, smoking, BMI, hypertension, and diabetes.


CONCLUSIONS
We report a new genetic variation (rs1805120) in the KCNH2 gene that predisposes Chinese Han individuals to the risk of acquired AF. Further genetic and functional studies are required to identify the etiological variants in linkage disequilibrium with this polymorphism.
Wang
Qun-Shan
QS
Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wang
Xiao-Feng
XF
Chen
Xing-Dong
XD
Yu
Jie-Fei
JF
Wang
Jun
J
Sun
Jian
J
Lu
Shang-Biao
SB
Shen
Mu-Yao
MY
Lu
Ming
M
Li
Yi-Gang
YG
Jin
Li
L
D000368:Aged; D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human