COPD病人差异性表达miRNAs与其骨质疏松及髋部骨折风险的临床关系分析

姜玉庆; 李文琪; 杨晓翠; 谢明明

COPD病人差异性表达miRNAs与其骨质疏松及髋部骨折风险的临床关系分析

Clinical relationship between differentially expressed miRNAs and the risk of osteoporosis and hip fracture in COPD patients

摘要

摘要:
目的： 探讨慢性阻塞性肺疾病（COPD）病人差异性表达miRNAs与其骨质疏松骨折风险的潜在关系。
方法： 选择36例有髋部骨折的骨质疏松症COPD病人，纳入骨质疏松髋部骨折（OHF）组和44例无髋部骨折的骨质疏松症COPD病人，纳入对照组。对2组病人的血液样本进行了初步的miRNA分析，检测2组之间有显著差异的miRNAs。然后进行聚合酶链反应的实时定量分析，以验证2组之间有显著差异的特定miRNAs。
结果： 与对照组相比，OHF组病人的支气管扩张器后肺活量百分比（FEV1%）、FEV1/强制生命容量（FVC）比值和25−羟基维生素D（25−（OH）VitD）明显降低（P ＜ 0.01），PINP明显增加（P ＜ 0.01）。在2组病人中检测到10个差异表达miRNAs，包括5个miRNAs下调（miR−21−5p、miR−28b−3p、miR−103a−3p、miR−122−5p、miR−125b−5p）和5个miRNAs上调（miR−31−5p、mi−143−3p、miR−23b−3p、miR−140−3p、miR−1）。miR−21−5p的相对表达水平与25−（OH）VitD的水平呈明显正相关关系（r = 0.518，P ＜ 0.01），与PINP的水平呈明显负相关关系（r = −0.547，P ＜ 0.01）。miR−31−5p的相对表达水平与25−（OH）VitD之间呈明显负相关关系（r = −0.388，P ＜ 0.01），与PINP之间呈明显正相关关系（r = 0.422，P ＜ 0.01）。ROC分析显示，miR−21−5p预测COPD骨质疏松症后髋部骨折的AUC为0.897，95%CI为0.828 ~ 0.966（P ＜ 0.01），miR−31−5p预测COPD骨质疏松症后髋部骨折的AUC为0.837，95%CI为0.744 ~ 0.930（P ＜ 0.01）。
结论： miR−21−5p和miR−31−5p可能参与COPD骨质疏松症病人髋部骨折的发生，是预测髋部骨折风险的潜在指标。

Abstract:
Objective To explore the potential relationship between differential expression of miRNAs in patients with chronic obstructive pulmonary disease (COPD) and their risk of osteoporotic fractures.
Methods This case-control study was conducted over a 2-year period (from May 2020). Thirty-six patients with osteoporotic COPD with hip fracture admitted to our hospital were selected to be included in the osteoporotic hip fracture (OHF) group, and 44 patients with osteoporotic COPD without hip fracture to be included in the control group. Blood samples from both groups were collected and subjected to an initial miRNA profiling to detect those miRNAs with significant variations based on polymerase chain reactions performed. A real-time quantitative polymerase chain reaction-based analysis was then performed for validation of specific miRNAs that were significantly different between the two groups.
Results Patients in the OHF group had significantly lower post-bronchodilator FEV1%, FEV1/FVC ratio and 25-(OH)VitD (P ＜ 0.05), and significantly increased PINP (P ＜ 0.05) compared to controls. Ten differentially expressed miRNAs were detected in both groups, including five miRNAs down-regulated (miR-21-5p, miR-28b-3p, miR-103a-3p, miR-122-5p, miR-125b-5p) and five miRNAs up-regulated (miR-31-5p, mi-143-3p, miR 23b-3p, miR-140-3p, miR-1). The relative expression levels of miR-21-5p were positively correlated with the levels of 25-(OH)VitD (r = 0.518, P ＜ 0.01), and negatively correlated with the levels of PINP (r = −0.547, P ＜ 0.01). miR-31-5p was positively correlated with the levels of 25-(OH)VitD (r = −0.547, P ＜ 0.01). miR-31-5p was negatively correlated with the levels of 25- (OH)VitD (r = −0.388, P ＜ 0.01), and a positive correlation with PINP (r = 0.422, P ＜ 0.01). ROC analysis showed that miR-21-5p predicted hip fracture after COPD osteoporosis with an AUC of 0.897, 95%CI of 0.828−0.966 (P ＜ 0.01), and miR-31-5p predicted an AUC of 0.837 and 95%CI of 0.744−0.930 (P ＜ 0.01) for hip fracture after COPD osteoporosis.
Conclusions miR-21-5p and miR-31-5p may be involved in the occurrence of hip fracture in patients with osteoporosis in COPD and predict the risk of hip fracture development. However, the conclusion of this study needs to be verified in the future large sample prospective study cohort.

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