Abstract
Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T > C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms.
Highlights
Coronary artery disease (CAD) is a devastating health disorder contributing to high morbidity and mortality rates worldwide [1]
MIAT gene expression dysregulation could have a potential diagnostic utility in coronary artery disease (CAD) patients as we reported in our previous study [13], and MALAT1 was involved in the proliferation of endothelial cells and associated with the progression of cardiovascular diseases [14]
All lipid profile parameters were significantly different between groups, with mean high-density lipoprotein (HDL) being higher in the control group (50 vs. 38 mg/dL) and LDL, total cholesterol, and triglycerides being higher in the study group (145, 221, and 182 mg/dL vs. 77, 168, and 95 mg/dL, respectively)
Summary
Coronary artery disease (CAD) is a devastating health disorder contributing to high morbidity and mortality rates worldwide [1]. Despite the continuous improvement in anti-ischemic drugs and coronary interventional techniques, CAD patients still suffer from many problems [3]. Long non-coding RNAs have caught the attention of several research groups attempting to define their role in human cells [5]. Numerous biological processes, such as epigenetic modifications, chromatin remodeling, splicing, and cellular differentiation, have been linked to lncRNAs, solidifying their status as critical genetic regulators [6]. Accumulating evidence indicates that lncRNA can play key roles in CAD, including disease diagnosis and/or prognosis [7–10]
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