Document Detail


Cx40 polymorphism in human atrial fibrillation.
MedLine Citation:
PMID:  16646598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown that two linked polymorphisms within regulatory regions of the gene for connexin40 (Cx40), at nucleotides -44 (G --> A) and +71 (A --> G) occur in about 7% of the general population. Cx40 is abundant in the atrium, and homozygosity for the linked polymorphisms combined with an SCN5A mutation appeared to be responsible for familial atrial standstill. We hypothesized that these polymorphisms are associated with the atrial electrophysiologic substrate favoring reentrant mechanisms for initiation of atrial fibrillation (AF). Reentry is promoted by spatial dispersion of refractoriness that can be expressed as a coefficient of dispersion (CD). METHODS: CD was calculated from the standard deviation of 12 local mean fibrillatory intervals recorded at right atrial sites during induced AF in 30 patients without structural heart disease (14 sporadic AF episodes, 16 no AF history). CD <or= 3.0 was considered normal. Cx40 genotypes were determined by DNA sequencing. RESULTS: Mean CD in AF patients was 5.96 +/- 0.70 and without AF 1.59 +/- 0.18 (p < 0.001). Thirteen of fourteen patients with AF had enhanced CD. Carriers of -44 AA genotype had higher CD compared with those with -44 GG genotype (6.37 +/- 1.21 vs. 2.38 +/- 0.39, p = 0.018), whereas heterozygotes showed intermediate values (3.95 +/- 1.38, NS). CONCLUSION: The rare linked Cx40 polymorphisms are associated with enhanced CD and thus with the substrate for reentry in AF.
Authors:
Richard N W Hauer; W Antoinette Groenewegen; Mehran Firouzi; Hemanth Ramanna; Habo J Jongsma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Advances in cardiology     Volume:  42     ISSN:  0065-2326     ISO Abbreviation:  Adv Cardiol     Publication Date:  2006  
Date Detail:
Created Date:  2006-05-01     Completed Date:  2006-07-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0270063     Medline TA:  Adv Cardiol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  284-91     Citation Subset:  IM    
Affiliation:
University Medical Center, Utrecht, The Netherlands. rhauer@azu.nl
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Atrial Fibrillation / genetics*,  therapy
Cardiac Pacing, Artificial
Connexins / genetics*
Electrophysiologic Techniques, Cardiac
Female
Genotype
Heart Atria / physiopathology
Humans
Male
Middle Aged
Polymorphism, Genetic*
Tachycardia, Supraventricular / genetics,  physiopathology
Chemical
Reg. No./Substance:
0/Connexins; 0/connexin 40

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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