1. A common connexin-40 gene promoter variant affects connexin-40 expression in human atria and is associated with atrial fibrillation
- Author
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Patrick T. Ellinor, Robert C. Wirka, John Barnard, Emelia J. Benjamin, Dan E. Arking, Mina K. Chung, Steven A. Lubitz, Kathryn L. Lunetta, Jonathan D. Smith, David R. Van Wagoner, Shamone Gore, and Alvaro Alonso
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Genotype ,TATA box ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Connexins ,Article ,Mice ,Young Adult ,Risk Factors ,Physiology (medical) ,Internal medicine ,Gene expression ,Atrial Fibrillation ,medicine ,SNP ,Animals ,Humans ,Myocytes, Cardiac ,Heart Atria ,Child ,Promoter Regions, Genetic ,Gene ,Cells, Cultured ,Aged ,Haplotype ,Promoter ,Middle Aged ,Minor allele frequency ,Endocrinology ,Haplotypes ,Case-Control Studies ,Models, Animal ,Female ,Cardiology and Cardiovascular Medicine - Abstract
Background— A common single-nucleotide polymorphism (SNP) in the promoter of the Connexin-40 (Cx40) gene GJA5 was suggested to affect Cx40 promoter activity and the risk of atrial fibrillation (AF), but the role of other common Cx40 polymorphisms is unknown. Methods and Results— Eight SNPs within the Cx40 gene region were tested for association with Cx40 levels measured in atrial tissue from 61 individuals. The previously described Cx40 promoter SNP (rs35594137, −44G→A) was not associated with Cx40 mRNA levels. However, a common SNP (rs10465885) located in the TATA box of an alternative Cx40 promoter was strongly associated with Cx40 mRNA expression ( P P P =0.046). This result was confirmed in a meta-analysis including 2 additional early-onset lone AF case-control cohorts (odds ratio, 1.16, P =0.022). rs35594137 was not associated with the lone AF phenotype in any of the cohorts studied or in a combined analysis. Conclusions— A previously described Cx40 promoter SNP was not found to influence Cx40 expression or risk of AF. We describe an alternate promoter polymorphism that directly affects levels of Cx40 mRNA in vivo and is associated with early-onset lone AF.
- Published
- 2010