2021
DOI: 10.1093/eurheartj/ehaa1108
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Abstract: Aims The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in … Show more

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Cited by 27 publications
(14 citation statements)
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“…This could be explained by the relatively complex architecture of the channels encoded by SCN5A genes, i.e., Nav1.5, (four homodomains, characterized each by six transmembrane regions with voltage sensitivity (S1-S4) and pore modulation (S5 and S6) [153]), thus mutations occurring in several genetic points could induce protein loss-of-function. Apart for these proteins, other related to the cell electrical activity (e.g., KCNE2, ankyrin-B adapter, PITX2, titin, calcium voltage-gated channels) and nuclear envelope (lamin A/C) were found associated with SSS when in genetic variance or polymorphism [154][155][156][157][158].…”
Section: Sss Due To Genetic Mutationsmentioning
confidence: 99%
“…This could be explained by the relatively complex architecture of the channels encoded by SCN5A genes, i.e., Nav1.5, (four homodomains, characterized each by six transmembrane regions with voltage sensitivity (S1-S4) and pore modulation (S5 and S6) [153]), thus mutations occurring in several genetic points could induce protein loss-of-function. Apart for these proteins, other related to the cell electrical activity (e.g., KCNE2, ankyrin-B adapter, PITX2, titin, calcium voltage-gated channels) and nuclear envelope (lamin A/C) were found associated with SSS when in genetic variance or polymorphism [154][155][156][157][158].…”
Section: Sss Due To Genetic Mutationsmentioning
confidence: 99%
“…42 43 A genome-wide association study of 6 469 sick sinus syndrome cases and more than a million controls revealed six loci associated to the disease. 44 Mendelian randomisation suggests a direct role of AF and lower heart rate in the development of sick sinus syndrome. 44 Angioedema is a known adverse drug reaction in individuals treated with antihypertensive ACE inhibitors.…”
Section: Other Contributionsmentioning
confidence: 99%
“…44 Mendelian randomisation suggests a direct role of AF and lower heart rate in the development of sick sinus syndrome. 44 Angioedema is a known adverse drug reaction in individuals treated with antihypertensive ACE inhibitors. A Danish study has found common variants located close to the bradykinin receptor B 2 gene to be associated with increased risk of developing angioedema related to treatment with ACE inhibitors.…”
Section: Other Contributionsmentioning
confidence: 99%
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“…Moreover, an update meta-analysis demonstrated that rs7193343 and rs2106261 were not associated with AF recurrence [ 11 ]. More recently, variants in ZFHX3 were also associated with sick sinus syndrome [ 12 ].…”
Section: Introductionmentioning
confidence: 99%