Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation

TY - JOUR

T1 - Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation

AU - Seifert, Mariam B.

AU - Olesen, Morten S.

AU - Christophersen, Ingrid E.

AU - Nielsen, Jonas B.

AU - Carlson, Jonas

AU - Holmqvist, Fredrik

AU - Tveit, Arnljot

AU - Haunsø, Stig

AU - Svendsen, Jesper H.

AU - Platonov, Pyotr G.

PY - 2019

Y1 - 2019

N2 - Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities. Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical. Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333. Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.

AB - Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities. Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical. Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333. Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.

KW - atrial fibrillation

KW - P-wave morphology

KW - SNP

U2 - 10.1111/anec.12661

DO - 10.1111/anec.12661

M3 - Journal article

C2 - 31152482

AN - SCOPUS:85066630349

SN - 1082-720X

VL - 24

JO - Annals of Noninvasive Electrocardiology

JF - Annals of Noninvasive Electrocardiology

IS - 6

M1 - e12661

ER -