Abstract
ObjectivesMicroRNAs (miRNAs) are short single-stranded RNAs that play a role in the post-transcriptional regulation of gene expression. Their deregulation can be associated with various diseases, such as cancer, neurodegenerative, and immune-related diseases. The aim of our study was to compare miRNA levels in plasma that could potentially influence the progression of hyperuricemia to gout, since the mechanism of progression is still unclear.MethodsTotal RNA, including miRNA, was isolated from the plasma of 45 patients with asymptomatic hyperuricemia, 131 patients with primary gout (including 16 patients having a gout attack), and 130 normouricemic controls. The expression of 18 selected miRNAs (cel-miR-39 and cel-miR-54 as spike-in controls, hsa-miR-16-5p and hsa-miR-25-3p as endogenous controls, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-30a-3p, hsa-miR-30c-5p, hsa-miR-126-3p, hsa-miR-133a-3p, hsa-miR-142-3p, hsa-miR-143-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-222-3p, hsa-miR-223-3p, hsa-miR-488-3p and hsa-miR-920) was measured using qPCR.ResultsWe found that hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-30c-5p, hsa-miR-142-3p, and hsa-miR-223-3p were significantly upregulated (p < 0.001) in the plasma of hyperuricemia and gout patients compared to normouricemic individuals. As part of the follow-up of our previous study, we found a negative correlation between hsa-miR-17-5p, hsa-miR-30c-5p, hsa-miR-126-3p, hsa-miR-142-3p, and hsa-miR-223-3p with plasma levels of chemokine MCP-1. Additionally, we found a positive correlation between CRP and plasma levels of hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-30c-5p, hsa-miR-126-3p, hsa-miR-142-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-222-3p, and hsa-miR-223-3p. Five of those miRNAs (hsa-miR-126-3p, hsa-miR-142-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-222-3p) also had a positive correlation with serum creatinine and therefore a negative correlation with eGFR.ConclusionFive miRNAs were significantly upregulated in the plasma of patients with hyperuricemia and gout (and those during a gout attack) compared to normouricemic controls. We also found a correlation between the plasma levels of several miRNA and plasma levels of MCP-1, CRP, serum creatinine, and eGFR.
Highlights
Uric acid is the end product of purine metabolism in the human body
We found a correlation between the plasma levels of several miRNA and plasma levels of Monocyte chemoattractant protein-1 (MCP-1), Creactive protein (CRP), serum creatinine, and Estimated glomerular filtration rate (eGFR)
Comparison of miRNA levels between studied groups We found five miRNAs that showed significantly decreased expression in the normouricemic cohort compared to hyperuricemic, gout, and gout attack patients, in most cases
Summary
Uric acid is the end product of purine metabolism in the human body. Hyperuricemia is caused by excessive production of uric acid (10% of cases) and/or reduced excretion (the majority of cases); about 10% of hyperuricemia cases escalate to clinically definable gout. There are risk factors for hyperuricemia and gout, e.g., lifestyle, metabolic syndrome, age, sex, and genetic predispositions. Major genes affecting uric acid excretion and reabsorption are ABCG2, respectively SLC2A9 and SLC22A12, which encode membrane transporters ABCG2, GLUT9, and URAT1. The most relevant gene that plays a role in hyperuricemia and gout is ABCG2. Variants Q126X (rs72552713) and Q141K (rs2231142) in the ABCG2 gene can cause severe dysfunction in this transporter and account for 90% of early-onset gout patients [2]. We published on the influence of nonsynonymous allelic variants, including functional characterizations, relative to the increased risk of gout progression [3, 4]
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