Atrial Fibrillation, Familial, 8

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

PITX2, NKX2-5, SCN2B, NKX2-6, SCN3B, ABCC9, KCNE2, NUP155, TTN, SCN5A, SCN4B, SCN1B, GATA4, NPPA, MYL4, KCNQ1, KCNJ2, KCNE1, KCNA5, GJA5, GATA6, GATA5

Drugs

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Description

Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997).

For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.

Mapping

Gudbjartsson et al. (2009) expanded the genomewide association study on atrial fibrillation in Iceland, which had identified risk variants on 4q25 (see 611494), and tested the most significant associations in samples from Iceland, Norway, and the United States. This sample consisted of 2,385 atrial fibrillation, or atrial flutter, cases and 33,752 controls who were genotyped using the Illumina HumanHap300 or HumanHapCNV370 bead chips. A variant in the ZFHX3 (104155) gene on chromosome 16q22, the T allele of single-nucleotide polymorphism (SNP) rs7193343, was associated significantly with atrial fibrillation (odds ratio 1.21, P = 1.4 x 10(-10)). This variant was also associated with ischemic stroke (odds ratio = 1.11, P = 0.00054) and cardioembolic stroke (odds ratio = 1.22, P = 0.00021) in a combined analysis of 5 stroke samples. The association of rs7193343 with atrial fibrillation was not significant in a Han Chinese population from Hong Kong consisting of 286 atrial fibrillation cases and 2,763 controls. However, the T allele at rs7193343 is much more frequent in the Han Chinese population than in samples from persons of European descent (0.68 vs 0.14-1.20, respectively).

Benjamin et al. (2009) conducted a metaanalysis of genomewide association studies for atrial fibrillation in participants from 5 community-based cohorts. Metaanalyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) atrial fibrillation cases identified a locus for atrial fibrillation at chromosome 16q22 represented by the SNP rs2106261 located in an intron of the ZFHX3 gene (risk ratio of 1.19; P = 2.3 x 10(-7)). This association was replicated in an independent cohort from the German Atrial Fibrillation Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined risk ratio for the 2 groups = 1.25; combined P = 1.8 x 10(-15)).