Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study

Abstract

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.

Circulating MicroRNAs as Specific Biomarkers in Atrial Fibrillation: A Meta-Analysis

“…However, defining miRNA-21 expression as tissue-specific is not possible because of the ambiguity about whether its variation in patients with AF is due to its expression in the atria. In addition, as shown in Table 1 , the authors found an association between increased expression of miRNA-133a and a 2% increase in the chance of developing AF [ 17 , 18 , 19 ].…”

“…Geurts et al [ 19 ] selected 1901 participants with incident AF, of whom 42.1% were men and 57.9% were women. Compared to the men, the women were older and non-smokers and exhibited more cases of hypertension and diabetes mellitus.…”

Circulating microRNAs as specific biomarkers in atrial fibrillation: A meta-analysis

“…The study by Geurts et al [19] was the only study to suggest miR-4798-3p and miR-20a-5p as markers of AF. miR-4798-3p presents negative results only among males; however, the mechanisms of interaction of this miRNA with AF are still unknown, and further studies are needed to elucidate these mechanisms.…”

“…The critical role of this miRNA in the development of AF is evident. It highlights the probability of a diagnosis of predisposition and early intervention for AF if the expression of this miRNA is high [19]. miRNA-21 also acts on TGF-β, increasing the brotic state [23].…”

“…Geurts et al [19] selected 1,901 participants with incident AF, of whom 42.1% were men and 57.9% were women. Compared to the men, women were older, non-smokers, and exhibited more cases of hypertension and diabetes mellitus.…”