Identification of a Genetic Locus for Familial Atrial Fibrillation

Brugada, Ramón; Tapscott, Terry; Czernuszewicz, Grazyna; Marian, Ali J.; Iglesias, Anna; Mont, Lluı́s; Brugada, Josép; Girona, Josep; Domingo, Anna; Bachinski, Linda L.; Roberts, Robert

doi:10.1056/nejm199703273361302

Cited by 500 publications

(257 citation statements)

References 11 publications

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“…Valvular heart disease may account for some of the residual lifetime risk for AF. 5,7,31 Several investigators have published associations between AF and specific genetic loci or alleles, [32][33][34] and there is ongoing interest in discovery of genetic determinants of AF. Tachy-brady or "sick sinus" syndrome and degenerative conduction system disease, which are poorly understood and for which there are no specific preventive modalities at present, also may account for a large proportion of incident AF.…”

Section: Discussionmentioning

confidence: 99%

Lifetime Risk for Development of Atrial Fibrillation

et al. 2004

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Background-Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. Conclusions-Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

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Section: Discussionmentioning

confidence: 99%

Lifetime Risk for Development of Atrial Fibrillation

et al. 2004

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“…An initial study by Brugada et al of a family in Spain and two other smaller families suggested possible linkage to chromosome 10q22-q24. 37 A 2003 study of a four-generation family with familial atrial fibrillation in Shandong Province, China implicated the KCNQ1 S140G missense mutation, with…”

Section: Disease Associationsmentioning

confidence: 99%

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Modell

Lehmann

2006

Genetics in Medicine

147

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Long QT syndrome (LQTS) refers to a group of "channelopathies"-disorders that affect cardiac ion channels. The "family" concept of syndromes has been applied to the multiple LQTS genotypes, LQT1-8, which exhibit converging mechanisms leading to QT prolongation and slowed ventricular repolarization. The 470ϩ allelic mutations induce loss-of-function in the passage of mainly K ϩ ions, and gain-of-function in the passage of Na ϩ ions through their respective ion channels. Resultant early after depolarizations can lead to a polymorphic form of ventricular tachycardia known as torsade de pointes, resulting in syncope, sudden cardiac death, or near-death (i.e., cardiac arrest aborted either spontaneously or with external defibrillation). LQTS may be either congenital or acquired. The genetic epidemiology of both forms can vary with subpopulation depending on the allele, but as a whole, LQTS appears in every corner of the globe. Many polymorphisms, such as HERG P448R and A915V in Asians, and SCN5A

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“…9 -11 There have been several reports addressing the genetic control of familial lone AF. [12][13][14] However, the genetic study of nonfamilial structural AF is scarce in the literature. On the basis of the aforementioned studies on RAS and AF, we hypothesized that RAS genes might be the susceptibility genes of nonfamilial structural AF and performed a genetic case-control study to demonstrate this.…”

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Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation

et al. 2004

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Background-The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. Methods and Results-A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected.The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls ( 2 ϭ62.5, Pϭ0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (Pϭ0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. Conclusions-This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

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Identification of a Genetic Locus for Familial Atrial Fibrillation

Cited by 500 publications

References 11 publications

Lifetime Risk for Development of Atrial Fibrillation

Lifetime Risk for Development of Atrial Fibrillation

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation

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