Atrial Fibrillation Associated Genetic Variants and Left Atrial Histology: Evaluation for Molecular Sub-Phenotypes

Autor:	Isaac R. Whitman, Pui-Yan Kwok, Jeffrey E. Olgin, Beverly Seiler, Gregory M. Marcus, Caroline Miller, Annie Poon, Anatalia Robles, Rachel A. Gladstone, Jingkun Yang, William A. LaFramboise, Thomas A. Dewland, James Longoria, Jason D. Roberts
Rok vydání:	2016
Předmět:	0301 basic medicine Pathology medicine.medical_specialty business.industry H&E stain Atrial fibrillation Single-nucleotide polymorphism Genome-wide association study Odds ratio 030204 cardiovascular system & hematology medicine.disease Logistic regression 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Fibrosis Physiology (medical) Medicine SNP Cardiology and Cardiovascular Medicine business
Zdroj:	Journal of Cardiovascular Electrophysiology. 27:1264-1270
ISSN:	1045-3873
DOI:	10.1111/jce.13083
Popis:	Introduction : Genome wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF), but the mechanisms underlying these relationships have not yet been elucidated. Inflammation and fibrosis have been posited as important mechanisms responsible for AF. We sought to investigate the impact of SNP carrier status on inflammation and fibrosis in left atrial appendage tissue. Methods and Results : Carrier status of 10 AF-associated SNPs was evaluated on DNA extracted from left atrial appendage tissue in 176 individuals (120 with AF). The presence of inflammation was evaluated through visual quantification of leukocyte infiltration following hematoxylin and eosin staining, while fibrosis was quantified using picrosirius red with fast green staining. Unadjusted and adjusted linear and logistic regression models were utilized to evaluate for an association between SNP carrier status and inflammation and fibrosis. On adjusted logistic regression analysis, the rs7164883 SNP (intronic within HCN4) was associated with a reduced odds of inflammation (odds ratio: 0.42; 95% CI: 0.22-0.81, p = 0.01), and was not associated with fibrosis on adjusted linear regression analysis (β-coefficient: -0.31; 95% CI: -1.03-0.40, p = 0.40). None of the remaining SNPs exhibited significant associations with left atrial inflammation or fibrosis. Conclusions : Among 10 AF-associated SNPs, a single genetic variant was associated with reduced left atrial inflammation, while no histologic differences were observed in the remaining 9. The known AF-associated SNPs do not appear to predispose to the development of pro-inflammatory or pro-fibrotic AF sub-phenotypes. This article is protected by copyright. All rights reserved
Databáze:	OpenAIRE
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