A potential risk factor of essential hypertension in case-control study: Circular RNA hsa_circ_0037911

Highlights

• Found a stable biomarker for early diagnosis of essential hypertension.

• Hsa_circ_0037911 is up-regulated in essential hypertension.

• CircRNAs causes essential hypertension through the concentration of Serum creatinine.

Abstract

Background

Essential hypertension (EH) is a high prevalence with multifactorial diseases. Human studies on the impact of genes on this disease are just in the initial stage, the mechanism of gene regulation is still remains unclear. Circular RNAs (circRNAs) as a continuous cycle of covalent closure, RNA molecules added to the 3′-5′ end covalently bound by the formation of incidental event. CircRNAs may be an important biomolecule in revealing the molecule regulate mechanisms of EH.

Methods

The circRNAs were selected and validated with qRT-PCR followed. Our experiment was conducted with case-control studies among 200 EH participants. The t-test was used to evaluate the different expression of circRNAs and miRNAs, the significance of which was set as p < 0.05.

Results

The hsa_circ_0037911 expression level in EH cases were significantly higher than healthy controls (p = 0.005). There was still important significance when adjusted by logistic regression (adjusted p = 0.026). We also found that hsa_circ_0037911 was an effective marker of EH (area under curve = 0.627; p = 0.002). The levels of hsa_circ_0037911 were significantly differences in gender, BMI, smoking and drinking among EH cases. There was a positive correlation between Serum creatinine (Scr) and hsa_circ_0037911.

Conclusions

Our findings suggested that higher expression hsa_circ_0037911 may be key circRNAs for EH development by changing the concentration of Scr and could be a stable biomarker for early diagnosis of EH.

Introduction

Essential hypertension (EH) is a complex multifactorial disorder that is one of the most common diseases among human cardiovascular system. The symptoms of EH are not obvious, so EH is known as a silent killer [1]. It is a global public crisis, and the prevalence rate of China is 32.5% [2], and about one third Chinese adults suffered EH. Although some of environmental risk factors for hypertension, including age, gender, region and socioeconomic status are reported [[3], [4], [5]], there are still considerable uncertain about the risk of EH, e.g. considerable of gene interactions. We also lack satisfactory biomarkers for early detection of EH. Therefore, it is necessary to determine the molecular characteristics and searching new diagnosis biomarkers of hypertension in current research.

Circular RNA (circRNA) is generally presented as a special class of endogenous RNAs characterized by lacking both a 5′cap and a 3′tail [6]. CircRNAs were thought to be a mysterious endogenous class of RNA transcribed from introns and exons [7,8], and were resistant to degradation caused by ribonuclease (RNase) or exonuclease.

Some studies have found that circRNAs expression were more abundant than classical mRNA, participate in the RNA - protein complex formation or RNR - RNA regulation network [9,10], and can serve as a template for virus and virus replication, as an intermediate in RNA processing reactions, as cis-acting transcriptional regulators such as snoRNAs and miRNA sponges [11]. Although recent studies indicate that circRNAs function participated in the development of some healthy diseases [12], little is known about their role in EH.

Hsa_circ_0037911is a circular RNA containing 4 exons by a length of 346nt splicing sequence (http://circrna.org/). The gene of circular RNA is located in the region from 11988810bp to 11991892bp of chromosome 16, and the association gene symbol is GSPT1 (G1 to S phase transition 1 gene). According to the bioinformatics analysis of the CircBase database, hsa_circ_0037911 is one of the circRNAs that may be associated with EH. In the present study, we chose it as the targeted circRNA for EH.

In this case-control study, it's the first time that we verified the expression levels of hsa_circ_0037911 in whole blood of participants is associated with EH. In addition, this is consistent with result of bioinformatics analysis of the CircBase database. Then, we explore the expression levels of hsa_circ_0037911 in EH group and control group, and the potential relationship between its expression levels and clinical indicators. Moreover, we have constructed a receiver operating characteristics (ROC) curve to analyze the sensitivity of hsa_circ_0037911in diagnosis of EH. Our data suggest that hsa_circ_0037911 plays a crucial role in the development of EH and may be a potential biomarker for hypertension screening and prevention.