Mariam B Seifert1,2, Morten S Olesen3,4, Ingrid E Christophersen5,6, Jonas B Nielsen3,4, Jonas Carlson1, Fredrik Holmqvist1, Arnljot Tveit6, Stig Haunsø3,4,7, Jesper H Svendsen3,4,7, Pyotr G Platonov1. 1. The Center for Integrative Electrocardiology, Arrhythmia Clinic Skåne University Hospital, Lund University (CIEL), Lund, Sweden. 2. Department of Cardiology, Frederiksberg Hospital, Copenhagen, Denmark. 3. Danish National Research Foundation Center for Cardiac Arrhythmia, Copenhagen, Denmark. 4. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. 5. The Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. 6. Department of Medical Research, Baerum Hospital, Vestre Viken Hospital Trust, Rud, Norway. 7. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Abstract
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.
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.
Authors: Mariam B Seifert; Morten S Olesen; Ingrid E Christophersen; Jonas B Nielsen; Jonas Carlson; Fredrik Holmqvist; Arnljot Tveit; Stig Haunsø; Jesper H Svendsen; Pyotr G Platonov Journal: Ann Noninvasive Electrocardiol Date: 2019-06-01 Impact factor: 1.468
Authors: Carlos Fernández-Hernando; Jun Yu; Alberto Dávalos; Jay Prendergast; William C Sessa Journal: Am J Pathol Date: 2010-06-25 Impact factor: 4.307
Authors: N Hagiwara; S E Klewer; R A Samson; D T Erickson; M F Lyon; M H Brilliant Journal: Proc Natl Acad Sci U S A Date: 2000-04-11 Impact factor: 11.205
Authors: Mariam B Seifert; Morten S Olesen; Ingrid E Christophersen; Jonas B Nielsen; Jonas Carlson; Fredrik Holmqvist; Arnljot Tveit; Stig Haunsø; Jesper H Svendsen; Pyotr G Platonov Journal: Ann Noninvasive Electrocardiol Date: 2019-06-01 Impact factor: 1.468