Key result
KCNN3 rs11264280 T allele linked to ~2.4-fold higher AF odds in hypertension.
Why the study?
Only a minority of hypertensive patients develop atrial fibrillation and the severity of target-organ damage varies widely at similar blood pressure. Whether common variants at established atrial fibrillation susceptibility loci relate to hypertensive target-organ damage as well as the arrhythmia itself was examined.
Do common genetic variants at PITX2, CAV1, and KCNN3 relate to atrial fibrillation and hypertensive target-organ damage in hypertensive patients of Uzbek ancestry?
Case-Control (n=372)
Single-blind (laboratory personnel blinded to case or control status)
No
Do common genetic variants at PITX2, CAV1, and KCNN3 relate to atrial fibrillation and hypertensive target-organ damage in hypertensive patients of Uzbek ancestry?
In hypertensive patients of Uzbek ancestry, variants at PITX2, CAV1, and 1q21/KCNN3 are strongly associated with atrial fibrillation, and the 1q21/KCNN3 variant rs11264280 is also associated with greater left ventricular mass and carotid intima-media thickness even in patients without atrial fibrillation.
Answers are grounded in this paper and cite their sources.
rs11264280 T allele may aid AF risk stratification in Central Asian hypertensives; extends KCNN3 loci to underrepresented groups but leaves adoption open pending validation.
Background Hypertension is the most prevalent modifiable risk factor for atrial fibrillation, yet only a minority of hypertensive patients develop the arrhythmia and the severity of target-organ damage varies widely at similar blood pressure. We examined whether common variants at established atrial fibrillation susceptibility loci relate to hypertensive target-organ damage as well as to the arrhythmia itself. Methods and Results In a single-centre case-control study, 372 patients with arterial hypertension of Uzbek ancestry (237 with and 135 without atrial fibrillation) were genotyped for five polymorphisms at PITX2, CAV1 and KCNN3 by real-time polymerase chain reaction. Associations with atrial fibrillation were tested by logistic regression under a log-additive model; associations with left ventricular mass index, carotid intima-media thickness, left atrial volume index and estimated glomerular filtration rate were tested by linear regression adjusted for age and systolic blood pressure. Three variants were associated with atrial fibrillation: rs6817105 (odds ratio 2.98 per C allele, 95% confidence interval 2.12–4.20), rs11264280 (2.38, 1.77–3.21) and rs11773845 (0.41, 0.30–0.57). Each rs11264280 T allele was also associated with a higher left ventricular mass index (5.51 g/m², 1.44–9.58) and a greater carotid intima-media thickness (0.05 mm, 0.02–0.08), and both associations were present in patients without atrial fibrillation. The rs11264280 effect allele was more frequent than in any 1000 Genomes super-population. Conclusions Genotype at the 1q21/KCNN3 locus may relate to the severity of hypertensive remodelling before the arrhythmia becomes manifest. These exploratory findings require replication in an independent cohort.
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Mashkurova et al. (2026) conducted a case-control in Arterial hypertension with and without atrial fibrillation (n=372). 1q21/KCNN3 rs11264280 T allele (along with PITX2 rs6817105 and CAV1 rs11773845 variants) vs. Reference/non-effect alleles in hypertensive controls without atrial fibrillation was evaluated on Association of 1q21-KCNN3 rs11264280 (T allele) with atrial fibrillation under a log-additive model (OR 2.38 per T allele, 95% CI 1.77-3.21, p=1.7 × 10⁻⁹). The 1q21/KCNN3 rs11264280 T allele increased atrial fibrillation odds (OR 2.38, 95% CI 1.77-3.21) and left ventricular mass index (+5.51 g/m²) in Uzbek patients with hypertension.
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