血管紧张素转化酶（ACE）水平，而不是 ACE 基因多态性，与 COVID-19 感染的预后相关：对糖尿病和高血压的影响。
Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension.
机构信息
Department of Endocrinology and Metabolism, Marmara University Faculty of Medicine, Istanbul, Turkey.
Department of Medical Genetics, Marmara University Faculty of Medicine, Istanbul, Turkey.
出版信息
PLoS One. 2023 Jul 11;18(7):e0288338. doi: 10.1371/journal.pone.0288338. eCollection 2023.
BACKGROUND
The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection.
METHODS
This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded.
RESULTS
A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001).
CONCLUSION
Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.
背景
肾素-血管紧张素-醛固酮系统在严重 COVID-19 感染中被证明被激活。我们旨在研究血管紧张素转换酶（ACE）水平、ACE 基因多态性、2 型糖尿病（T2DM）和高血压（HT）与 COVID-19 感染预后之间的关系。
方法
这项横断面研究分析了 SARS-CoV-2 感染的成年患者的临床特征。进行 ACE 基因分析和 ACE 水平测量。根据 ACE 基因多态性（DD、ID 或 II）、疾病严重程度（轻度、中度或重度）以及二肽基肽酶-4 酶抑制剂（DPP4i）、ACE 抑制剂（ACEi）或血管紧张素受体阻滞剂（ARB）的使用情况对患者进行分组。还记录了重症监护病房（ICU）入院和死亡率。
结果
共纳入 266 名患者。基因分析在 ACE 1 基因中检测到 DD 多态性在 32.7%（n = 87）、ID 在 51.5%（n = 137）和 II 在 15.8%（n = 42）的患者中。ACE 基因多态性与疾病严重程度、ICU 入院或死亡率无关。死亡（p = 0.004）或入住 ICU（p<0.001）的患者以及患有严重疾病的患者 ACE 水平高于患有轻度（p = 0.023）或中度（p<0.001）疾病的患者。HT、T2DM、ACEi/ARB 或 DPP4i 的使用与死亡率或 ICU 入院无关。患有 HT 的患者与无 HT 的患者 ACE 水平无差异（p = 0.374），使用 ACEi/ARB 的患者与不使用 ACEi/ARB 的患者 ACE 水平无差异（p = 0.999）。患有 T2DM 的患者与无 T2DM 的患者 ACE 水平无差异（p = 0.062），使用 DPP4i 治疗的患者与未使用 DPP4i 治疗的患者 ACE 水平无差异（p = 0.427）。ACE 水平是死亡率的弱预测指标，但却是 ICU 入院的重要预测指标。它可以预测总 ICU 入院（临界值>37.092ng/ml，AUC：0.775，p<0.001）。
结论
我们的研究结果表明，较高的 ACE 水平，但不是 ACE 基因多态性、ACEi/ARB 或 DPP4i 的使用，与 COVID-19 感染的预后相关。HT 和 T2DM 的存在以及 ACEi/ARB 或 DPP4i 的使用与死亡率或 ICU 入院无关。
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