doi: 10.7150/ijms.67815

Potential Genes Associated with COVID-19 and Comorbidity

Supplementary Material

Supplementary file.

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^{College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.}

^{Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, Sichuan, China.}

^{Department of medical Laboratory, The General Hospital of Western Theater Command, Chengdu, China.}

^{Chengdu Medical College, Chengdu, China.}

^{School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China.}

^{Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, China.}

^{Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.}

^{Department of Pharmacy, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, China.}

✉ Corresponding authors: Xu Jia, E-mail: nc.ude.cmc@uxaij; Ling Zhang, E-mail: nc.ude.ujz@nadufnilgnahz; Jinlin Guo, E-mail: nc.ude.mctudc@695oug; Fengling Qiao: moc.qq@602939969.

*These authors contributed equally in this manuscript.

Competing Interests: The authors have declared that no competing interest exists.

Received 2021 Oct 7; Accepted 2022 Jan 5.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Abstract

Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.

Keywords: COVID-19, comorbidity, bioinformatics, susceptibility gene, disease severity, SARS-CoV-2

Abstract

Notes: Count value represents the number of target genes that core genes belong to in the term, and p was corrected by Benjamini-Hochberg method. And q value was estimated for false discovery rate control. The values p < 0.01 and q < 0.01 were considered statistically significant.

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Acknowledgments

We acknowledge all the participants in the Non-coding RNA and Drug Discovery Key Laboratory for helpful discussions and Editage for English language editing.

Author Contributions

Xu Jia, Jinlin Guo, Fengling Qiao, and Lin Zhang designed the study. All authors contributed to their thoughts and advice. Shanshan Feng and Fuqiang Song wrote the manuscript. The manuscript has been reviewed by Xianqin Zhang. All authors participated in the final version of the article and supported this submission.

Data availability statement

The authors confirm that some data supporting the study's findings are available in the article and supplementary materials.

Acknowledgments

Abbreviations

GO	Gene Ontology
KEGG	Kyoto Encyclopedia of Genes and Genomes
NLRP	NOD-like receptor protein
PPI	protein-protein interaction
TMPRSS2	transmembrane serine protease 2
TLR	Toll-like receptor
RBD	receptor-binding domain
ROS	reactive oxygen species
CRAC	Ca^{release-activated Ca}^channels
RAAS	renin-angiotensin-aldosterone system
ACE	angiotensin-converting enzyme
ARDS	acute respiratory distress syndrome

Abbreviations

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