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

• Published in: BMC medical genomics Vol. 13; no. 1; p. 184
• Main Authors: Tibaut, Miha, Mankoč Ramuš, Sara, Petrovič, Daniel
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-12-2020; BioMed Central; BMC
• Subjects: Acute coronary syndromes; Aged; Alleles; Allelomorphism; Angina pectoris; Angiography; Arteries; Atherosclerosis; Biomarker; Cardiovascular disease; Case-Control Studies; Cholesterol; Comorbidity; Complications and side effects; Computed tomography; Coronary artery; Coronary artery disease; Coronary heart disease; Coronary Stenosis - diagnostic imaging; Coronary Stenosis - epidemiology; Coronary Stenosis - genetics; Coronary Stenosis - surgery; Coronary vessels; Cross-Sectional Studies; Development and progression; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Endarterectomy; Enzymes; Female; Gene polymorphism; Genetic analysis; Genetic aspects; Genetic Markers; Genetic polymorphism; Genetic polymorphisms; Genetic Predisposition to Disease; Health aspects; Heart attack; Heart diseases; Humans; Male; Medical research; Medicine, Experimental; Membrane proteins; Membrane Proteins - genetics; Middle Aged; Mitochondrial Proteins - genetics; Myocardial infarction; Myocardial Infarction - etiology; Oxidative Stress; Polymorphism; Polymorphism, Single Nucleotide; Reactive oxygen species; Reactive oxygen species modulator 1; Retrospective Studies; Risk factors; Slovenia - epidemiology; Statistical analysis; Stenosis; Triglycerides; Type 2 diabetes; White People - genetics; Slovenia; Germany; Reactive oxygen species modulator 1; Biomarker; Coronary artery disease; Diabetes mellitus; Genetic polymorphism
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-020-00845-3

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).
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.
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.
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.