Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success.
BACKGROUND
Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF.


RESULTS
We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10(-16); PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10(-11); ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10(-14); KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation.


CONCLUSIONS
SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea (E.K.C.).
Eue-Keun
EK
Choi
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Jae Hyung
JH
Park
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Ji-Young
JY
Lee
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Chung Mo
CM
Nam
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Min Ki
MK
Hwang
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Jae-Sun
JS
Uhm
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Boyoung
B
Joung
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Young-Guk
YG
Ko
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Moon-Hyoung
MH
Lee
Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA (S.A.L., P.T.E.) Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (S.A.L., P.T.E.).
Steven A
SA
Lubitz
Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA (S.A.L., P.T.E.) Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (S.A.L., P.T.E.).
Patrick T
PT
Ellinor
Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea (J.H.P., J.Y.L., C.M.N., M.K.H., J.S.U., B.J., Y.G.K., M.H.L., H.N.P.).
Hui-Nam
HN
Pak
D000368:Aged; D044466:Asian People / Q000235:genetics; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D016022:Case-Control Studies; D017115:Catheter Ablation / Q000009:adverse effects; D016009:Chi-Square Distribution; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000503:physiopathology / Q000601:surgery*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012008:Recurrence; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C406328:KCNN3 protein, human; C071660:ZFHX3 protein, human
atrial fibrillation; catheter ablation; genetic polymorphism; phenotype; recurrence