title: Atrial Fibrillation Associated Genetic Variants and Left Atrial Histology: Evaluation for Molecular Sub-Phenotypes.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Jason D
authors: JD
authors: Roberts
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Jingkun
authors: J
authors: Yang
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Rachel A
authors: RA
authors: Gladstone
authors: Division of Cardiovascular Surgery, Sutter Health, Sacramento, California, USA.
authors: James
authors: J
authors: Longoria
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Isaac R
authors: IR
authors: Whitman
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Thomas A
authors: TA
authors: Dewland
authors: Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
authors: Caroline
authors: C
authors: Miller
authors: Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
authors: Anatalia
authors: A
authors: Robles
authors: Cardiovascular, Research Institute, University of California San Francisco, San Francisco, California, USA.
authors: Annie
authors: A
authors: Poon
authors: Division of Cardiovascular Surgery, Sutter Health, Sacramento, California, USA.
authors: Beverly
authors: B
authors: Seiler
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: William A
authors: WA
authors: Laframboise
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Jeffrey E
authors: JE
authors: Olgin
authors: Cardiovascular, Research Institute, University of California San Francisco, San Francisco, California, USA.
authors: Pui-Yan
authors: PY
authors: Kwok
authors: Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Gregory M
authors: GM
authors: Marcus
keywords: atrial fibrillation; fibrosis; genetics; inflammation