The C allele of the reactive oxygen species modulator 1 (ROMO1) polymorphism rs6060566 is a biomarker predicting coronary artery stenosis in Slovenian subjects with type 2 diabetes mellitus

Abstract

Background We aimed to examine the role of the rs6060566 polymorphism of the reactive oxygen species modulator 1 (ROMO1) gene in the development of myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM). Methods A total of 1072 subjects with T2DM were enrolled in this cross-sectional case–control study: 335 subjects with MI and 737 subjects without clinical signs of coronary artery disease (CAD). The genetic analysis of the rs6060566 polymorphism was performed in all subjects. To assess the degree of coronary artery obstruction, a subpopulation of 128 subjects with T2DM underwent coronary computed tomography angiography. Next, endarterectomy samples were obtained during myocardial revascularization from diffusely diseased coronary arteries in 40 cases, which were analysed for ROMO1 expression according to their genotype. Results There were no statistically significant associations between different genotypes or alleles of the rs6060566 polymorphism and MI in subjects with T2DM. The carriers of the C allele of the ROMO1 rs6060566 had a threefold increased likelihood of having 50–75% coronary artery stenosis (Adjusted OR = 3.27, 95% CI 1.16–9.20). Subjects with two affected coronary arteries had a 3.72 fold higher prevalence of MI (OR = 3.72, 95% CI 1.27–10.84). With CAD in LMCA or LAD, MI prevalence was about 3.5-fold higher (p = 0.07 for LMCA and p = 0.01 for LAD). Furthermore, the carriers of the rs6060566 C allele showed higher number of positive cells for ROMO1 expression in endarterectomy samples of coronary arteries. Conclusions According to our study, the rs6060566 polymorphism of the ROMO1 gene is not a risk factor for MI in Caucasians with T2DM. However, we found that subjects carrying the C allele were at a 3.27-fold increased risk of developing severe CAD compared with those who had non-obstructive CAD. Moreover, C allele carriers showed a statistically higher number of cells positive for ROMO1 compared with T allele carriers in coronary endarterectomy samples.

Review of microRNAs and lncRNAs in atherosclerosis, diabetes, and other inflammatory conditions

“…One of the crucial cytokines involved in the pathogenesis of psoriasis and RA, IL-17, has been reported to play an important role in the production of reactive oxygen species (ROS) [10,20]. ROS are on the list of factors that can cause endothelial dysfunction [6]. IL-17 is one of the main factors for endothelial dysfunction in patients with RA [21].…”

“…Endothelial dysfunction causes changes in the production of endothelial cells (i.e. expression of adhesion molecules, ROMO1 expression and production of inflammatory cytokines…), and they lead to morphological changes in the vessel wall (inflammation, atherosclerotic changes) [1,2,6]. IL-1β, IL-6, IL-17, TNF-α and hs-CRP are involved in the pathogenesis of atherosclerosis, psoriasis and RA [23,24].…”

“…Elevated circulating markers such as C-reactive protein (CRP), interleukins (IL) (IL-1β, IL-6, IL-8, IL-12, IL-17, IL-32, IL-36), tumor necrosis factor α (TNFα), and vascular endothelial growth factor (VEGF) are commonly found in conditions of lowgrade inflammation, such as CVD, psoriasis, RA, and DM [3][4][5]. Immune cells of innate or adaptive immunity (monocytes, neutrophils, mast cells, macrophages, and lymphocytes) are thought to play an important role in chronic inflammation [6]. Moreover, they were reported to be responsible for the production of inflammatory cytokines [3][4][5].…”

A Review of MicroRNAs and lncRNAs in Atherosclerosis as Well as Some Major Inflammatory Conditions Affecting Atherosclerosis

“…Elevated circulating markers such as C-reactive protein (CRP), interleukins (IL) (IL-1β, IL-6, IL-8, IL-12, IL-17, IL-32, IL-36), tumor necrosis factor α (TNFα), and vascular endothelial growth factor (VEGF) are commonly found in conditions of low-grade inflammation, such as CVD, psoriasis, RA, and diabetes mellitus (DM) [ 4 , 5 , 6 ]. Immune cells of innate or adaptive immunity (monocytes, neutrophils, mast cells, macrophages, and lymphocytes) are thought to play an important role in chronic inflammation [ 6 , 7 ]. Moreover, they were reported to be responsible for the production of inflammatory cytokines [ 4 , 5 , 6 ].…”

Identification of oxidative stress-related genes and potential mechanisms in atherosclerosis

“…As of now, genome-wide association studies have identified more than 50 independent loci associated with cardiovascular diseases that collectively account for 13.3% of their heritability ( Nikpay et al, 2015 ). One study investigated the role of oxidative stress ROM O 1 gene polymorphism and showed that subjects carrying the C allele were at a more than three folds increased risk of developing cardiovascular diseases ( Tibaut et al, 2020 ). Therefore, an in-depth exploration of oxidative stress will help us understand how this disease develops and will also provide new ideas for its prevention and treatment.…”