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COVID-19 患者的二肽基肽酶-4 水平和 DPP4 基因多态性。与疾病和严重程度的关系。

Dipeptidylpeptidase-4 levels and DPP4 gene polymorphisms in patients with COVID-19. Association with disease and with severity.

机构信息

Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.

Departament of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.

出版信息

Life Sci. 2021 Jul 1;276:119410. doi: 10.1016/j.lfs.2021.119410. Epub 2021 Mar 24.

DOI:10.1016/j.lfs.2021.119410
PMID:33774023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7989663/
Abstract

BACKGROUND

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes de COVID-19 disease use as a principal receptor the angiotensin-converting enzyme-2 (ACE2). It has been suggested that dipeptidyl peptidase-4 (DPP4) can be another possible receptor for this virus. The present study aimed to establish if the DPP4 levels and DPP4 polymorphisms are associated with COVID-19 disease and its severity.

METHODS

The study included 107 COVID-19 patients and 263 matched-healthy controls. Fifty patients required invasive mechanical ventilation. The DPP4 was quantified in serum using the Bioplex system. Based on the previous results and the functional prediction analysis, we select for the study 5 DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, rs3788979, and rs17574) and these were determined using the 5´exonuclease TaqMan assays.

RESULTS

Low levels of DPP4 were observed in COVID-19 patients (46.5 [33.1-57.7] ng/mL) when compared to healthy controls (125.3 [100.3-157.3] ng/mL) (P < 0.0001). Also, patients that required mechanical ventilation showed lower DPP4 levels (42.8 [29.8-56.9] ng/mL) than those that did not need this procedure (49.2 [39.9-65.6] ng/mL) (P = 0.012). DPP4 levels correlated negatively with age, fibrinogen, and platelet levels, and positively with albumin, alanine aminotransferase, and percentage of neutrophils. The DPP4 rs3788979 polymorphism was associated with a high risk of COVID-19 disease and, the TT genotype carriers had the lowest DPP4 levels.

CONCLUSIONS

In summary, in the present study, an association of low levels of DPP4 with COVID-19 disease and severity was found. The association of the DPP4 rs3788979 polymorphism with COVID-19 is also reported.

摘要

背景

引起 COVID-19 疾病的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)主要利用血管紧张素转换酶 2(ACE2)作为受体。有人认为二肽基肽酶 4(DPP4)可能是该病毒的另一种可能的受体。本研究旨在确定 DPP4 水平和 DPP4 多态性是否与 COVID-19 疾病及其严重程度相关。

方法

本研究纳入了 107 例 COVID-19 患者和 263 名匹配的健康对照者。50 例患者需要接受有创机械通气。使用 Bioplex 系统定量检测血清中的 DPP4。基于先前的结果和功能预测分析,我们选择了 5 个 DPP4 多态性(rs12617336、rs12617656、rs1558957、rs3788979 和 rs17574)进行研究,并使用 5´exonuclease TaqMan assays 进行测定。

结果

与健康对照组(125.3 [100.3-157.3] ng/mL)相比,COVID-19 患者的 DPP4 水平较低(46.5 [33.1-57.7] ng/mL)(P < 0.0001)。此外,需要机械通气的患者的 DPP4 水平(42.8 [29.8-56.9] ng/mL)低于不需要该程序的患者(49.2 [39.9-65.6] ng/mL)(P = 0.012)。DPP4 水平与年龄、纤维蛋白原和血小板水平呈负相关,与白蛋白、丙氨酸氨基转移酶和中性粒细胞百分比呈正相关。DPP4 rs3788979 多态性与 COVID-19 疾病的高风险相关,TT 基因型携带者的 DPP4 水平最低。

结论

综上所述,本研究发现 DPP4 水平与 COVID-19 疾病及其严重程度相关。还报道了 DPP4 rs3788979 多态性与 COVID-19 的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/04ce65c84619/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/01ea40a15a06/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/610275070b75/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/010038347a96/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/451d5c41b1a4/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/04ce65c84619/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/01ea40a15a06/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/610275070b75/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/010038347a96/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/451d5c41b1a4/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/7989663/04ce65c84619/gr5_lrg.jpg

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