Disrupted Expression of Circadian Clock Genes in Patients with Bronchial Asthma.
Disrupted Expression of Circadian Clock Genes in Patients with Bronchial Asthma.
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DOI：
10.2147/jaa.s302508
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发表时间：
2021
影响因子：
3.2
通讯作者：
Yang MY
中科院分区：
文献类型：
--
作者：
Chen HC;Chen YC;Wang TN;Fang WF;Chang YC;Chen YM;Chen IY;Lin MC;Yang MY
生物钟通过昼夜节律与昼夜24小时同步，昼夜节律的正常运作对许多生理过程至关重要。昼夜节律的破坏可以影响疾病的进程，并影响疾病的严重程度，治疗反应，甚至生存。在这项回顾性病例对照研究中，我们试图探讨支气管哮喘患者的昼夜节律钟基因表达是否受到干扰。我们采用实时定量逆转录-聚合酶链反应检测了120例哮喘患者和60名健康人外周血总白细胞中9种核心生物钟基因（BMAL 1、CK 1 ε、CLOCK、PER 1、PER 2、PER 3和TIM）的表达。9个生物钟基因的表达水平在哮喘患者和健康人之间存在显著差异，但与哮喘控制状况无关。我们还注意到PER 3表达在有和无夜间症状的哮喘患者中的差异。在控制良好的哮喘患者中，有夜间症状的患者BMAL 1、CK 1 ε、CLOCK、CK 11、CK 12和PER 1的表达显著低于无夜间症状的患者。然而，在控制不佳的哮喘患者中，只有BMAL 1、CK 1 ε、PER 1和PER 2的表达在有夜间症状和无夜间症状的患者之间存在显著差异。Logistic回归分析显示，BMAL 1、CKIε、PER 3和TIM 4个基因的联合表达可提高预测哮喘的能力（AUC=0.924; 95% CI=0.875-0.958; P<0.001）。我们的研究结果显示，支气管哮喘患者的生物钟基因表达改变，夜间症状患者的PER 3表达下调。在有或无夜间症状的哮喘患者中，在控制良好或控制不好的亚组中也观察到昼夜节律钟基因表达的改变。BMAL 1、CKIε、PER 3和TIM的联合表达可能是支气管哮喘的潜在预测因子。
Circadian clock is synchronized to the 24-hour day by the daily light–dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma. We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ε, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals. Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ε, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ε, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIε, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875–0.958; P<0.001). Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIε, PER3, and TIM could be a potential predictor for bronchial asthma.