Genetic Variants of AGO1*rs595961 and AGO2*rs4961280 with Susceptibility to Bladder Carcinoma

The microRNA (miRNA) biogenesis mechanism remains elusive, yet various genetic variants may play a role in predicting the biological function of this machinery system and its association with the advancement of specific tumors. This study aimed to investigate the relationship between AGO1 and AGO2 gene variants with the elevated risk of bladder carcinoma (BLCA) using genetic, biochemical, and bioinformatic approaches. This retrospective study comprised of 252 participants [122 BLCA patients and 130 cancer-free controls], matched for age and gender. The AGO1*rs595961 and AGO2*rs4961280 genetic variants were characterized using TaqMan genotyping assay. A bioinformatics framework, stratification analysis, and multivariate regression were employed. The genetic distribution of AGO1*rs595961 was associated with an increased risk of bladder carcinoma under allelic (OR = 1.50, p = 0.026) and recessive (OR = 2.01, p = 0.010) models. In contrast, the AGO2*rs4961280 variant demonstrated no considerable association with bladder carcinoma progression under various genetic models (p > 0.05). An in-depth examination of AGO1 and AGO2 protein revealed their involvement in gene silencing by miRNA, post-transcriptional gene silencing, regulatory RNA binding, and positive regulation of mRNA catabolic processes. The AGO1*rs595961 genetic variant was correlated with an elevated risk of bladder carcinoma, whereas the AGO2*rs4961280 variant was not. Further research is warranted to understand the underlying molecular mechanisms and potential clinical implications.