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碳酸酐酶 IX 作为阻塞性睡眠呼吸暂停疾病严重程度的标志物。

Carbonic Anhydrase IX as a Marker of Disease Severity in Obstructive Sleep Apnea.

机构信息

Department of Chest Diseases, Malatya Turgut Özal University, Malatya 44210, Turkey.

Department of Biochemistry, Malatya Turgut Özal University, Malatya 44210, Turkey.

出版信息

Medicina (Kaunas). 2022 Nov 14;58(11):1643. doi: 10.3390/medicina58111643.

Abstract

Background and Objectives: Carbonic anhydrase (CA) enzymes are a family of metalloenzymes that contain a zinc ion in their active sites. CA enzymes have been implied in important situations such as CO2 transport, pH regulation, and oncogenesis. CA-IX is a transmembrane glycoprotein and stimulates the expression of hypoxia-inducible factor-1 (HIF-1) CA-IX. This study aimed to determine serum CA-IX levels in OSA patients in whom intermittent hypoxia is important and to investigate the relationship between serum CA-IX levels and disease severity. Materials and Methods: The study included 88 people who applied to Malatya Turgut Özal University Training and Research Hospital Sleep Disorders Center without a history of respiratory disease, malignancy, and smoking. Patients were divided into three groups: control (AHI < 5, n = 31), mild−moderate OSA (AHI = 5−30, n = 27) and severe OSA (AHI > 30, n = 30). The analysis of the data included in the research was carried out with the SPSS (IBM Statistics 25, NY, USA). The Shapiro−Wilk Test was used to check whether the data included in the study had a normal distribution. Comparisons were made with ANOVA in multivariate groups and the t-test in bivariate groups. ANCOVA was applied to determine the effect of the CA-IX parameter for OSA by controlling the effect of independent variables. The differentiation in CA-IX and OSA groups was analyzed regardless of BMI, age, gender, and laboratory variables. ROC analysis was applied to determine the parameter cut-off point. Sensitivity, specificity, and cut-off were calculated, and the area under the curve (AUC) value was calculated. Results: Serum CA-IX levels were 126.3 ± 24.5 pg/mL in the control group, 184.6 ± 59.1 pg/mL in the mild−moderate OSA group, and 332.0 ± 39.7 pg/mL in the severe OSA group. Serum CA-IX levels were found to be higher in the severe OSA group compared to the mild−moderate OSA group and control group and higher in the mild−moderate OSA group compared to the control group (p < 0.001, p < 0.001, p < 0.001, respectively). In addition, a negative correlation between CA-IX and minimum SaO2 and mean SaO2 (r = −0.371, p = 0.004; r = −0.319, p = 0.017, respectively). A positive correlation between CA-IX and desaturation index (CT90) was found (r = 0.369, p = 0.005). A positive correlation was found between CA-IX and CRP (r = 0.340, p = 0.010). When evaluated by ROC curve analysis, the area under the curve (AUC) value was determined as 0.940 (95% CI 0.322−0.557; p < 0.001). When the cut-off value for CA-IX was taken as 254.5 pg/mL, it was found to have 96.7% sensitivity and 94.8% specificity in demonstrating severe OSA. Conclusions: Our study found that serum CA-IX value was higher in OSA patients than in control patients, and this elevation was associated with hypoxemia and inflammation. CA-IX value can be a fast, precise, and useful biomarker to predict OSA.

摘要

背景与目的

碳酸酐酶(CA)酶是一类含有锌离子的金属酶,其活性部位含有锌离子。CA 酶在 CO2 运输、pH 调节和肿瘤发生等重要情况下发挥作用。CA-IX 是一种跨膜糖蛋白,可刺激缺氧诱导因子-1(HIF-1)CA-IX 的表达。本研究旨在确定间歇性低氧血症在 OSA 患者中重要的情况下,血清 CA-IX 水平,并探讨血清 CA-IX 水平与疾病严重程度之间的关系。

材料与方法

本研究纳入了 88 名无呼吸系统疾病、恶性肿瘤和吸烟史的患者,他们向马拉蒂亚图尔古特奥扎尔大学培训和研究医院睡眠障碍中心就诊。患者分为三组:对照组(AHI<5,n=31)、轻度-中度 OSA(AHI=5-30,n=27)和重度 OSA(AHI>30,n=30)。研究中包含的数据的分析是使用 SPSS(IBM Statistics 25,NY,USA)进行的。Shapiro-Wilk 检验用于检查研究中包含的数据是否具有正态分布。在多元组中使用 ANOVA 进行比较,在二元组中使用 t 检验进行比较。通过控制独立变量的影响,应用 ANCOVA 确定 CA-IX 参数对 OSA 的影响。无论 BMI、年龄、性别和实验室变量如何,都对 CA-IX 和 OSA 组进行了分析。应用 ROC 分析确定参数截断值。计算了灵敏度、特异性和截断值,并计算了曲线下面积(AUC)值。

结果

对照组血清 CA-IX 水平为 126.3±24.5pg/ml,轻度-中度 OSA 组为 184.6±59.1pg/ml,重度 OSA 组为 332.0±39.7pg/ml。与轻度-中度 OSA 组和对照组相比,重度 OSA 组的血清 CA-IX 水平更高,与轻度-中度 OSA 组相比,对照组的血清 CA-IX 水平更高(p<0.001,p<0.001,p<0.001,分别)。此外,CA-IX 与最低 SaO2 和平均 SaO2 呈负相关(r=-0.371,p=0.004;r=-0.319,p=0.017,分别)。发现 CA-IX 与饱和度指数(CT90)呈正相关(r=0.369,p=0.005)。发现 CA-IX 与 CRP 呈正相关(r=0.340,p=0.010)。通过 ROC 曲线分析,确定曲线下面积(AUC)值为 0.940(95%CI 0.322-0.557;p<0.001)。当 CA-IX 的截断值为 254.5pg/ml 时,其在显示重度 OSA 方面具有 96.7%的灵敏度和 94.8%的特异性。

结论

我们的研究发现,OSA 患者的血清 CA-IX 值高于对照组患者,这种升高与低氧血症和炎症有关。CA-IX 值可以作为预测 OSA 的快速、精确和有用的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56d2/9695925/5af3fbd9a26c/medicina-58-01643-g001.jpg

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