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

Seifert, Mariam B. LU ; Olesen, Morten S.; Christophersen, Ingrid E.; Nielsen, Jonas B.; Carlson, Jonas LU ; Holmqvist, Fredrik LU ; Tveit, Arnljot; Haunsø, Stig; Svendsen, Jesper H. and Platonov, Pyotr G. LU (2019) In Annals of Noninvasive Electrocardiology
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,... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
atrial fibrillation, P-wave morphology, SNP
in
Annals of Noninvasive Electrocardiology
publisher
Wiley-Blackwell
external identifiers
  • scopus:85066630349
ISSN
1082-720X
DOI
10.1111/anec.12661
language
English
LU publication?
yes
id
9383eab9-d25e-41ce-aaed-543801529fa3
date added to LUP
2019-06-25 14:25:05
date last changed
2019-07-09 04:49:37
@article{9383eab9-d25e-41ce-aaed-543801529fa3,
  abstract     = {<p>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 &lt;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 &lt; 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.</p>},
  articleno    = {e12661},
  author       = {Seifert, Mariam B. and Olesen, Morten S. and Christophersen, Ingrid E. and Nielsen, Jonas B. and Carlson, Jonas and Holmqvist, Fredrik and Tveit, Arnljot and Haunsø, Stig and Svendsen, Jesper H. and Platonov, Pyotr G.},
  issn         = {1082-720X},
  keyword      = {atrial fibrillation,P-wave morphology,SNP},
  language     = {eng},
  month        = {06},
  publisher    = {Wiley-Blackwell},
  series       = {Annals of Noninvasive Electrocardiology},
  title        = {Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation},
  url          = {http://dx.doi.org/10.1111/anec.12661},
  year         = {2019},
}