Dataset Information

Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation.

ABSTRACT:

Background

Diagnosis of atrial fibrillation (AF) can be difficult, requiring cumbersome investigations. We aimed to determine the association of established whole-blood gene expression scores with prevalent AF and to evaluate their performance for the identification of AF in a SIRS (Steroids in Cardiac Surgery) trial cohort.

Methods and results

Whole-blood, transcriptome-wide gene expression profiling was performed using the Illumina HumanHT-12 Expression BeadChip in 416 participants (65% men) before surgery, including 91 with a diagnosis of AF. An AF gene score (GS) calculated from 7 genes reported to be upregulated in AF and a validated GS for biological age based on 1254 genes related to aging were both independently associated with AF diagnosis before surgery in multivariate logistic regression analyses adjusting for known risk factors (P=0.0006 and P=0.003). Addition of AF and biological age GSs to clinical risk factors led to significant improvement in area under the receiver operating characteristic curve (from 0.77 to 0.80; P=0.03), continuous net reclassification improvement index (P<0.0001), and integrated discrimination improvement index (P=0.0002). When stratifying AF by subtype, AF GS was mainly associated with paroxysmal AF (P=0.003), whereas the biological age GS was mainly associated with permanent AF (P=0.017).

Conclusions

We validated the existence of a blood gene expression signature for prevalent AF and showed that biological age derived from gene expression is significantly associated with prevalent AF. These findings suggest a potential utility of blood gene expression for the identification of patients with AF, particularly paroxysmal AF. This result could have implications for the prevention and management of cryptogenic stroke.

Clinical trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00427388.

SUBMITTER: Theriault S

PROVIDER: S-EPMC5586311 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation.

Thériault Sébastien S Whitlock Richard R Raman Kripa K Vincent Jessica J Yusuf Salim S Paré Guillaume G

Journal of the American Heart Association 20170630 7

<h4>Background</h4>Diagnosis of atrial fibrillation (AF) can be difficult, requiring cumbersome investigations. We aimed to determine the association of established whole-blood gene expression scores with prevalent AF and to evaluate their performance for the identification of AF in a SIRS (Steroids in Cardiac Surgery) trial cohort.<h4>Methods and results</h4>Whole-blood, transcriptome-wide gene expression profiling was performed using the Illumina HumanHT-12 Expression BeadChip in 416 participa ...[more]

PMID: 28666990

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Project description:PurposeTo investigate the expression profiles of long noncoding RNAs (lncRNAs) in patients with atrial fibrillation (AF).MethodsThe peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs from 2017.01 to 2017.08. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways.ResultsThere were 19 lncRNAs differentially expressed (FC ≥ 2, P < 0.05), of which 6 were upregulated and 13 were downregulated. Two of three upregulated lncRNAs (P = 0.014 and 0.006 for HNRNPU-AS1 and LINC00861, respectively) and two of three downregulated lncRNAs (P = 0.028 and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT-PCR and showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process, and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen, and cytoplasm. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding, and molecular function. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks.ConclusionsThe expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play an important role in the pathophysiology and mechanisms of AF.

Dataset Information

Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation.

Background

Methods and results

Conclusions

Clinical trial registration

Publications

Gene Expression Profiles for the Identification of Prevalent Atrial Fibrillation.

Similar Datasets

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