The inverted pattern of circulating miR-221-3p and miR-222-3p associated with isolated low HDL-C phenotype

• Published in: Lipids in health and disease Vol. 17; no. 1; p. 188
• Main Authors: Zhou, Yuntao, Liu, Mengdi, Li, Jinrong, Wu, Bing, Tian, Wei, Shi, Lu, Zhang, Jing, Sun, Zening
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.08.2018; BioMed Central; BMC
• Subjects: Analysis; Cardiovascular disease; Cardiovascular diseases; Circulating microRNAs; Clinical translation; Diagnosis; Genetic aspects; High density lipoprotein; High density lipoproteins; Investigations; Isolated risk phenotype; Lipids; MicroRNA; miRNA; Obesity; Phenotypes; Physiological aspects; Risk factors; China; Clinical translation; Cardiovascular disease; Circulating microRNAs; Isolated risk phenotype
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-018-0842-1

We investigated the baseline characterization of cardiovascular disease (CVD)-derived circulating miR-221-3p/222-3p in isolated low HDL-C phenotype (ILHP) to enhance our understanding on their molecular pathological pattern prior to disease onset. We screened 174 asymptomatic subjects with isolated low HDL-C phenotype (n = 88) and normal lipid phenotype (n = 86), and detected circulating levels of CVD-derived circulating miR-221-3p/222-3p using TaqMan miRNA Real-time PCR detection system. We found the inverted pattern of decreased circulating miR-221-3p (0.415 [0.249, 1.004] vs 0.658 [0.347, 1.534], p = 0.002) versus increased miR-222-3p levels (0.379 [0.101, 0.701] vs 0.156 [0.043, 0.407], p < 0.001) in ILHP. The baseline levels of circulating miR-221-3p and miR-222-3p are correlated with serum HDL-C levels (miR-221-3p: r = 0.306, p < 0.001; miR-222-3p: r = - 0.201, p = 0.008). Gender-based analysis showed female-specific elevation of circulating miR-221-3p in asymptomatic individual. Multiple logistic regression analysis showed that circulating miR-222-3p is robustly independent factor (adjusted OR = 8.42, 95%CI: 2.53-27.98, p < 0.001) and significantly improved the performance of the predictive clinical model distinguished ILHP from normal lipid phenotype (AUC: 0.816, 95%CI (0.754, 0.879) vs AUC: 0.771, 95%CI (0.702, 0.840); Z = 2.169, p = 0.030). Moreover, the increased original Ct ratio of miR-221-3p to miR-222-3p in male ILHP (1.003 [0.927, 1.063] vs 0.927 [0.858, 0.967], p < 0.001) significantly enhanced the ability to classify male ILHP compared with the male predictive clinical model (AUC: 0.851, 95%CI (0.770, 0.933) vs AUC: 0.759, 95%CI (0.659, 0.859); Z = 2.474, p < 0.05). The inverted pattern of circulating miR-221-3p and miR-222-3p are potentially clinically actionable signature for molecular pathology in isolated low HDL-C phenotype.