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A common connexin-40 gene promoter variant affects connexin-40 expression in human atria and is associated with atrial fibrillation.

TitleA common connexin-40 gene promoter variant affects connexin-40 expression in human atria and is associated with atrial fibrillation.
Publication TypeJournal Article
Year of Publication2011
AuthorsWirka RC, Gore S, Van Wagoner DR, Arking DE, Lubitz SA, Lunetta KL, Benjamin EJ, Alonso A, Ellinor PT, Barnard J, Chung MK, Smith JD
JournalCirc Arrhythm Electrophysiol
Volume4
Issue1
Pagination87-93
Date Published2011 Feb
ISSN1941-3084
KeywordsAdolescent, Adult, Aged, Animals, Atrial Fibrillation, Case-Control Studies, Cells, Cultured, Child, Connexins, Female, Genotype, Haplotypes, Heart Atria, Humans, Male, Mice, Middle Aged, Models, Animal, Myocytes, Cardiac, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Young Adult
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

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.

DOI10.1161/CIRCEP.110.959726
Alternate JournalCirc Arrhythm Electrophysiol
PubMed ID21076161
PubMed Central IDPMC3057452
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
T32 HL007575-26A1 / HL / NHLBI NIH HHS / United States
HL090620 / HL / NHLBI NIH HHS / United States
UL1 RR024989 / RR / NCRR NIH HHS / United States
R21 DA027021 / DA / NIDA NIH HHS / United States
1RC1HL099452 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
UL1 RR025005-05 / RR / NCRR NIH HHS / United States
U01 HG004402-01 / HG / NHGRI NIH HHS / United States
R01 HL104156 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
1UL-RR024989 / RR / NCRR NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
T32 HL007575 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL059367-10 / HL / NHLBI NIH HHS / United States
RC1 HL099452 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
RC1 HL101056 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
R01 HL090620 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
R01 HL087641-03 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
R01 HL086694-03 / HL / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
UL1 RR024989-05 / RR / NCRR NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DA027021 / DA / NIDA NIH HHS / United States
T32HL007575 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
RC1 HL099452-02 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
R01 HL092577-03 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R21 DA027021-02 / DA / NIDA NIH HHS / United States
RC1 HL101056-02 / HL / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
HL092577 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01 HL090620-04 / HL / NHLBI NIH HHS / United States