Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups

Alzahrani, Zain; Ornelas-Loredo, Aylin; Darbar, Sara D.; Farooqui, Abdullah; Mol, Denise; Chalazan, Brandon; Villagrana, Nancy E.; McCauley, Mark D.; Lazar, Sorin; Wißner, Erik; Bhan, Adarsh; Konda, Sreenivas; Darbar, Dawood

doi:10.1001/jamanetworkopen.2018.2497

Cited by 27 publications

(23 citation statements)

References 26 publications

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“…35 Recent work from the same group sequencing 60 candidate genes from Black and odds of having a first-degree family member with AF than White patients, supporting genetic predispositions that should be further explored. 37 Whether environmental or genetic, there appear to be ethnic-specific factors that either protect Black patients from AF or make White patients more prone to AF. 38 Although genetics cannot fully account for the differential AF risk across races, its role with or without the contribution of ascertainment bias in AF detection by race warrants further investigation as it could provide important insight into the AF paradox in the Black population.…”

Section: Marcus Et Al Studied White and African American Patients Of European Ancestry From Cardiovascularmentioning

confidence: 99%

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Racial and Ethnic Differences in the Management of Atrial Fibrillation

et al. 2021

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Section: Marcus Et Al Studied White and African American Patients Of European Ancestry From Cardiovascularmentioning

confidence: 99%

“… 36 Black and Hispanic patients with early-onset AF have been found to have higher odds than White patients of having a first-degree family member with AF, supporting genetic predispositions that should be further explored. 37 …”

Section: Genetics Of Afmentioning

confidence: 99%

Racial and Ethnic Differences in the Management of Atrial Fibrillation

et al. 2021

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“…More than 44 disease‐causing genes with rare damaging mutations have been identified in monogenic forms of familial AF. In addition, over 95 genetic loci have been identified by genome wide association studies of AF (Alzahrani et al, 2018). The pathophysiology of the distinct clinical entity characterized by AF and slowing of conduction along the electrical conduction system is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction

et al. 2021

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The genetic causes of atrial fibrillation (AF) with slow conduction are unknown. Eight kindreds with familial AF and slow conduction, including a family affected by early‐onset AF, heart block, and incompletely penetrant nonischemic dilated cardiomyopathy (DCM) underwent whole exome sequencing. A known pathogenic mutation in the desmin (DES) gene resulting in p.S13F substitution (NM_001927.3:c.38C>T) at a PKC phosphorylation site was identified in all four members of the kindred with early‐onset AF and heart block, while only two developed DCM. Higher penetrance for AF and heart block prompted a genetic screening for DES modifier(s). A deleterious mutation in the phosphodiesterase‐4D‐interacting‐protein (PDE4DIP) gene resulting in p.A123T substitution (NM_001002811:c.367G>A) was identified that segregated with early‐onset AF, heart block, and the DES mutation. Three additional novel deleterious PDE4DIP mutations were identified in four other unrelated kindreds. Characterization of PDE4DIPA123T in vitro suggested impaired compartmentalization of PKA and PDE4D characterized by reduced colocalization with PDE4D, increased cAMP activation leading to higher PKA phosphorylation of the β2‐adrenergic‐receptor, and decreased PKA phosphorylation of desmin after isoproterenol stimulation. Our findings identify PDE4DIP as a novel gene for slow AF and unravel its epistatic interaction with DES mutations in development of conduction disease and arrhythmia.

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“…A high proportion (14.8%) of patients with AF, as shown in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registry, had a family history of AF (FAF) 5 . It is well established that patients with FAF are susceptible to AF 6–11 . Mutation‐induced electrical and structural remodeling, such as shortened action potential duration, reduced conduction velocity, and increased tissue vulnerability, may facilitate the initiation and maintenance of AF 12 .…”

Section: Introductionmentioning

confidence: 99%

Effect of family history of atrial fibrillation on recurrence after atrial fibrillation ablation: A report from the Chinese Atrial Fibrillation Registry Study

Jiang

et al. 2021

Cardiovasc electrophysiol

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Background To evaluate the impact of family history of atrial fibrillation (FAF) on postablation atrial tachyarrhythmia (AT) recurrence. Methods All the 8198 patients undergoing initial AF ablation registered in the Chinese Atrial Fibrillation Registry study were analyzed. FAF was defined as having first‐degree relatives diagnosed as AF at age 65 years or younger, and before the time the case in this study was diagnosed. Cox proportional hazards models were used to evaluate the impact of FAF on postablation AT recurrence. Age, sex, body mass index, AF type, history of congestive heart failure, hypertension, diabetes mellitus, prior stroke/transient ischemic attack/systemic embolism, vascular diseases, use of contact force‐sensing catheter, and completion of high school were adjusted. The definition of AT recurrence was any documented AF, atrial flutter, or AT lasting more than or equal to 30 s after 3 months blanking period. Results After a mean follow‐up of 26.2 ± 19.6 months, 318 out of the 645 patients (49.3%) with FAF and 3339 out of the 7553 patients (44.2%) without FAF experienced AT recurrence, corresponding to annual recurrence rates of 22.8% and 20.2%, respectively. Patients with FAF had a significant higher risk of AT recurrence (adjusted hazard ratio 1.129, 95% confidence interval 1.005–1.267) in multivariable analysis. Moreover, FAF had a significant higher impact on AT recurrence in the subgroup of patients diagnosed with AF at age 50 years or younger (p for interaction = .036). Conclusion FAF is a risk factor for postablation AT recurrence. This is especially true in those with AF diagnosed at 50 years or younger.

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Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups

Cited by 27 publications

References 26 publications

Racial and Ethnic Differences in the Management of Atrial Fibrillation

Racial and Ethnic Differences in the Management of Atrial Fibrillation

Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction

Effect of family history of atrial fibrillation on recurrence after atrial fibrillation ablation: A report from the Chinese Atrial Fibrillation Registry Study

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