Analysis of MicroRNA Processing Machinery Gene DROSHA, DICER1, and XPO5 Variants Association with Atherosclerosis: A Case–control Study

Abstract Background: Atherosclerosis, a primary cause of coronary artery disease, involves chronic inflammatory arterial changes and contributes significantly to global vascular mortality. Genetic variations, especially single-nucleotide polymorphisms (SNPs) within microRNA (miRNA) machinery genes, impact miRNA biogenesis and play roles in atherosclerosis pathogenesis and progression. This study aimed to investigate the association between SNPs in DROSHA rs10719, DICER rs1057035 , and XPO5 rs11077 as potential risk factors for atherosclerosis. Methods: The study included 100 individuals with clinically diagnosed atherosclerosis (mean age: 53 ± 7 years) and 100 control subjects (mean age: 52 ± 7 years). Genomic DNA was extracted and genotyped using real-time TaqMan allelic discrimination assays for DROSHA rs10719, DICER rs1057035 , and XPO5 rs11077 SNPs. Results: The recessive model of DROSHA rs10719 , particularly the GG genotype, showed a significant six-fold increased risk of atherosclerosis (adjusted odds ratio [AOR] 6.35, 95% confidence interval [CI] = 1.53–26.26, P = 0.0059). Conversely, the GG genotype of XPO5 rs11077 was more prevalent in controls (24% vs. 13%) and associated with reduced risk (OR = 0.39, 95% CI = 0.178–0.845, P = 0.019). In the recessive model, the GG genotype of XPO5 rs11077 remained protective (AOR = 0.14, 95% CI = 0.02–1.12, P = 0.04), consistent with findings from the log additive model (AOR = 0.27, 95% CI = 0.08–0.87, P = 0.016). Combinations of alleles involving DICER1 rs1057035, XPO5 rs11077 , and DROSHA rs10719 (T-G-G, T-G-A, and C-T-A) were also associated with reduced risk of developing atherosclerosis ( P < 0.05). Conclusion: This study highlights the association of specific SNPs in DROSHA and XPO5 genes with susceptibility to atherosclerosis, providing insights into the genetic factors that may contribute to the development and progression of these cardiovascular diseases.