ArticlePediatric research2026
MiR-182-5p, miR-122-5p and hsa-piR-28004 as indicators of disease and treatment in pediatric familial hypercholesterolemia.
Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundFamilial hypercholesterolemia (FH) is the most common inborn metabolic disease, characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased risk for premature cardiovascular disease (CVD). Non-coding RNAs (ncRNAs) are promising biomarkers in CVD, but their role in pediatric FH remains unclear. We investigated circulating ncRNAs in pediatric heterozygous FH (heFH), focusing on lipid-lowering regimens and cardiovascular risk.
methodsFifty-one heFH patients and 17 controls (age 5-19 years) were prospectively enrolled and fasting serum and clinical data, including carotid intima-media thickness (cIMT) and echocardiography, collected. Small RNA sequencing was followed by targeted qPCR validation of candidate ncRNAs. Subgroup analyses compared newly diagnosed, diet-treated, and pharmacological lipid-lowering therapy (LLT)-obtaining patients. Additionally, miRNAs formerly described as atherosclerosis-associated were assessed.
resultsMiR-182-5p (p = 0.012) and hsa-piR-28004 (p = 0.024) were significantly downregulated in newly diagnosed heFH patients vs. controls. MiR-122-5p was significantly upregulated in patients under LLT compared to both newly diagnosed patients (p = 0.037) and controls (p = 0.013). Hsa-piR-28004 expression levels correlated with oxidized LDL (r = 0.345, p = 0.005), HDL-C (r = -0.282; p = 0.023) and cIMT (r ≈ -0.34, p = < 0.01).
conclusionMiR-182-5p and hsa-piR-28004 may serve as early indicators of disease, independent of traditional risk factors. Upregulation of miR-122-5p under LLT suggests involvement in treatment response. IMPACT: This is the first comprehensive profiling of both microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) in children and adolescents with heterozygous familial hypercholesterolemia (heFH). Circulating miR-182-5p, miR-122-5p and hsa-piR-28004 are potential early indicators of disease and treatment response in pediatric heFH. MiRNAs identified to be associated with atherosclerosis in adults are not robustly expressed in pediatric heFH, underscoring age-specific molecular differences. These findings support the potential of non-coding RNAs (ncRNAs) as non-invasive biomarkers for improved diagnosis, monitoring, and personalized risk assessment in children and adolescents with heFH beyond traditional lipid metrics.
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