Significant Association of rs13376333 in KCNN3 on Chromosome 1q21 With Atrial Fibrillation in a Taiwanese Population

Chang, Shui-Feng; Chang, Sheng Nan; Hwang, Juey‐Jen; Chiang, Fu-Tien; Tseng, Chuen Den; Lee, Jen Kuang; Lai, Ling‐Ping; Lin, Jiunn Lee; Wu, Cho Kai; Tsai, Chia Ti

doi:10.1253/circj.cj-11-0525

Cited by 25 publications

(10 citation statements)

References 29 publications

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“…Among them, variants near the PITX2 gene show the strongest association with AF; an association that has been independently replicated in other ethnic populations, including our Taiwanese population 5. An association of KCNN3 with AF was also found in our Taiwanese population 6. However, many of these strong risk variants are still very far from the coding regions of their nearby linked genes, and the true disease-causing variants remain unknown.…”

Section: Introductionsupporting

confidence: 65%

Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

et al. 2014

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Section: Introductionsupporting

confidence: 65%

Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

et al. 2014

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“…Interest in I KCa as a therapeutic target for atrial arrhythmias followed reports of a genetic predisposition to lone AF attributed to a single nucleotide mutation in the gene KCNN3, which encodes for SK3. [40] , [41] The exact mechanism(s) by which a single mutation affects SK channel function remains unclear. Data supporting both loss of function and gain of function as possible mechanisms for AF have been reported in multiple models.…”

Section: Discussionmentioning

confidence: 99%

Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure

et al. 2014

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The role of IKCa in cardiac repolarization remains controversial and varies across species. The relevance of the current as a therapeutic target is therefore undefined. We examined the cellular electrophysiologic effects of IKCa blockade in controls, chronic heart failure (HF) and HF with sustained atrial fibrillation. We used perforated patch action potential recordings to maintain intrinsic calcium cycling. The IKCa blocker (apamin 100 nM) was used to examine the role of the current in atrial and ventricular myocytes. A canine tachypacing induced model of HF (1 and 4 months, n = 5 per group) was used, and compared to a group of 4 month HF with 6 weeks of superimposed atrial fibrillation (n = 7). A group of age-matched canine controls were used (n = 8). Human atrial and ventricular myocytes were isolated from explanted end-stage failing hearts which were obtained from transplant recipients, and studied in parallel. Atrial myocyte action potentials were unchanged by IKCa blockade in all of the groups studied. IKCa blockade did not affect ventricular myocyte repolarization in controls. HF caused prolongation of ventricular myocyte action potential repolarization. IKCa blockade caused further prolongation of ventricular repolarization in HF and also caused repolarization instability and early afterdepolarizations. SK2 and SK3 expression in the atria and SK3 in the ventricle were increased in canine heart failure. We conclude that during HF, IKCa blockade in ventricular myocytes results in cellular arrhythmias. Furthermore, our data suggest an important role for IKCa in the maintenance of ventricular repolarization stability during chronic heart failure. Our findings suggest that novel antiarrhythmic therapies should have safety and efficacy evaluated in both atria and ventricles.

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“…2,3 Familial cases of AF underscore a genetic basis for disease, 4 and research has implicated mutations and polymorphisms in the development of AF. 5 Recently, several common genetic variants have been shown to be associated with AF in genomewide association studies performed in populations of European ancestry [6][7][8][9][10] ; however, ethnic differences exist in the frequency of AF-related single nucleotide polymorphisms (SNPs) between European and Asian populations, 11,12 and thus the relationship between these SNPs and AF in non-European populations remains unclear. Furthermore, despite the identification of these AF-associated loci, data regarding the association between variants at these loci and clinical outcomes remain limited.…”

mentioning

confidence: 99%

Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

Choi

Park

Lee

et al. 2015

JAHA

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BackgroundGenomewide 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.Methods and ResultsWe 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.ConclusionsSNPs 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.

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Significant Association of rs13376333 in KCNN3 on Chromosome 1q21 With Atrial Fibrillation in a Taiwanese Population

Cited by 25 publications

References 29 publications

Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Calcium-Activated Potassium Current Modulates Ventricular Repolarization in Chronic Heart Failure

Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

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