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Background  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.    Methods  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.    Results  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).    Conclusions  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.    Electronic supplementary material  The online version of this article (10.1186/s12944-018-0842-1) contains supplementary material, which is available to authorized users.

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