Tangshan Key Laboratory of Clinical Molecular Diagnosis and Treatment, Tangshan Gongren Hospital, No. 27 Wenhua Road, Tangshan, Hebei, 063000, People's Republic of China.
Lipids Health Dis. 2018 Aug 16;17(1):188. 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.
我们研究了心血管疾病（CVD）衍生的循环 miR-221-3p/222-3p 在孤立性低 HDL-C 表型（ILHP）中的基线特征，以增强我们在疾病发作前对其分子病理模式的理解。
我们筛选了 174 名无症状的孤立性低 HDL-C 表型（n=88）和正常脂质表型（n=86）患者，使用 TaqMan miRNA 实时 PCR 检测系统检测 CVD 衍生的循环 miR-221-3p/222-3p 的水平。
我们发现，ILHP 中循环 miR-221-3p 的水平降低（0.415[0.249,1.004] vs 0.658[0.347,1.534]，p=0.002），而 miR-222-3p 的水平升高（0.379[0.101,0.701] vs 0.156[0.043,0.407]，p<0.001）。循环 miR-221-3p 和 miR-222-3p 的基线水平与血清 HDL-C 水平相关（miR-221-3p：r=0.306，p<0.001；miR-222-3p：r=-0.201，p=0.008）。基于性别的分析显示，女性无症状个体中循环 miR-221-3p 升高。多因素逻辑回归分析显示，循环 miR-222-3p 是独立的强预测因子（调整 OR=8.42，95%CI：2.53-27.98，p<0.001），并显著改善了预测临床模型区分 ILHP 与正常脂质表型的性能（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）。此外，男性 ILHP 中 miR-221-3p 与 miR-222-3p 的原始 Ct 比值增加（1.003[0.927,1.063] vs 0.927[0.858,0.967]，p<0.001），与男性预测临床模型相比，显著提高了男性 ILHP 的分类能力（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）。
循环 miR-221-3p 和 miR-222-3p 的倒置模式可能是孤立性低 HDL-C 表型分子病理的潜在临床可操作特征。
