Genetics of atrial fibrillation.
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ABSTRACT:
SUBMITTER: Lubitz SA
PROVIDER: S-EPMC3073057 | biostudies-literature | 2010 Apr
REPOSITORIES: biostudies-literature
Publications
Genetics of atrial fibrillation.
Lubitz Steven A SA Yi B Alexander BA Ellinor Patrick T PT
Heart failure clinics 20100401 2
Recent studies of atrial fibrillation (AF) have identified mutations in a series of ion channels; however, these mutations appear to be relatively rare causes of AF. A genome-wide association study has identified novel variants on chromosome 4 associated with AF, although the mechanism of action for these variants remains unknown. Ultimately, a greater understanding of the genetics of AF should yield insights into novel pathways, therapeutic targets, and diagnostic testing for this common arrhyt ...[more]
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Project description:Recent studies of atrial fibrillation (AF) have identified mutations in a series of ion mutations; however, these channels appear to be relatively rare causes of AF. Recent genome-wide association studies for AF have identified novel variants associated with the disease, although the mechanism of action for these variants remains unknown. Ultimately, a greater understanding of the genetics of AF should yield insights into novel pathways, therapeutic targets, and diagnostic testing for this common arrhythmia.
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Project description:Background Atrial fibrillation ( AF ) is a common arrhythmia seen in clinical practice. Occasionally, no common risk factors are present in patients with this arrhythmia. This suggests the potential underlying role of genetic factors associated with predisposition to developing AF . Methods and Results We conducted a comprehensive review of the literature through large online libraries, including PubMed. Many different potassium and sodium channel mutations have been discussed in their relation to AF . There have also been non-ion channel mutations that have been linked to AF . Genome-wide association studies have helped in identifying potential links between single-nucleotide polymorphisms and AF . Ancestry studies have also highlighted a role of genetics in AF . Blacks with a higher percentage of European ancestry are at higher risk of developing AF . The emerging field of ablatogenomics involves the use of genetic profiles in their relation to recurrence of AF after catheter ablation. Conclusions The evidence for the underlying role of genetics in AF continues to expand. Ultimately, the role of genetics in risk stratification of AF and its recurrence is of significant interest. No established risk scores that are useful in clinical practice are present to date.
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Project description:Purpose of reviewAtrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.Recent findingsGenome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many implicated genes. Genetic variants at identified loci also help predict individual atrial fibrillation risk and response to different therapies.SummaryContinued advances in the field of genetics and molecular biology have led to significant insight into the genetic underpinnings of atrial fibrillation. Potential clinical applications of these studies include the identification of new therapeutic targets and development of genetic risk scores to optimize management of this common cardiac arrhythmia.
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Project description:Atrial fibrillation (AF) is the most common persistent cardiac dysrhythmia and the number one cause of arrhythmia-related hospitalizations. In addition, AF is a major contributor to stroke. With life expectancies increasing, the growing global disability from AF has crippling implications for society. Several family studies have shown a strong polygenetic predisposition for AF but, so far, most of the linkage analysis and candidate gene studies have discovered only monogenic, rare, deleterious mutations. Recent breakthroughs in high-throughput genotyping technology have allowed improved scanning of the genome with greater statistical power to detect susceptibility alleles for AF. Using this technology, a region on 4q25 has now been identified and validated in thousands of cases as a common susceptibility factor for AF with an odds ratio of over 3.0 for homozygotes. The Paired-like homeodomain transcription factor 2 (PITX2) gene, which is involved in embryonic cardiac development, has now been identified as the causal variant for the 4q25 susceptibility locus. Additional susceptibility variants are anticipated that will have direct ramifications for prognosis and treatment of this highly pervasive and clinically significant disorder.
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