Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study
Haixia Wang, Zhiyun Zhang, Li Xie, Kongli Lu, Shuyi Zhang, Shunpeng Xing
BMC Pulmonary Medicine, doi:10.1186/s12890-024-03013-w
Background The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population.
Methods The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results.
Results The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW.
Conclusions We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.
Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s12890-024-03013-w.
Supplementary Material 1 Supplementary Material 2 Author contributions HW and ZZ: data collection and statistical analysis, LX: statistical analysis and manuscript revision, HW, ZZ and KL: manuscript preparation,SZ and SX: study design and supervision, all authors: manuscript revision. All authors contributed to the article and approved the submitted version.
Declarations Ethical approval and informed consent Not applicable.
Consent to publish Not applicable.
Competing interests The authors have no relevant financial or non-financial interests to disclose.
Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Allenby, Bocquel, Saunders, Kazmer, Speck et al., Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids, Proc Natl Acad Sci
Burgess, Butterworth, Thompson, Mendelian randomization analysis with multiple genetic variants using summarized data, Genet Epidemiol
Burgess, Thompson, Collaboration, Avoiding bias from weak instruments in mendelian randomization studies, Int J Epidemiol
Burgess, Thompson, Interpreting findings from mendelian randomization using the MR-Egger method, Eur J Epidemiol
Chow, Gale, Loo, RIG-I and other RNA sensors in antiviral immunity, Annu Rev Immunol
Das, Thapa, Karki, Das, Mahapatra et al., Retinoic acid signaling pathways in development and diseases, Bioorg Med Chem
Ghyselinck, Duester, Retinoic acid signaling pathways, Development
Green, Mellanby, Vitamin a as an anti-infective Agent, Br Med J
Initiative, Mapping the human genetic architecture of COVID-19, Nature
Initiative, The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic, Eur J Hum Genet
Jovic, Ali, Ibrahim, Jessop, Tarassoli et al., Could vitamins help in the fight against COVID-19?, Nutrients
Kamat, Blackshaw, Young, Surendran, Burgess et al., PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations, Bioinformatics
Kawai, Akira, Toll-like receptor and RIG-I-like receptor signaling, Ann N Y Acad Sci
Kumar, Zuo, Yalavarthi, Hunker, Knight et al., SARS-CoV-2 spike protein S1-Mediated endothelial Injury and pro-inflammatory state is amplified by Dihydrotestosterone and prevented by Mineralocorticoid antagonism, Viruses
Majumder, Minko, Recent developments on therapeutic and diagnostic approaches for COVID-19, AAPS J
Mora, Iwata, Von Andrian, Vitamin effects on the immune system: vitamins A and D take centre stage, Nat Rev Immunol
Nhieu, Milbauer, Lerdall, Najjar, Wei et al., Targeting Cellular Retinoic Acid binding protein 1 with retinoic acid-like compounds to mitigate Motor Neuron Degeneration, Int J Mol Sci
Rehman, Rehman, Yoo, COVID-19 challenges and its therapeutics, Biomed Pharmacotherapy = Biomedecine Pharmacotherapie
Rohani, Mozaffar, Mesri, Shokri, Delaney et al., Evaluation and comparison of vitamin A supplementation with standard therapies in the treatment of patients with COVID-19, East Mediterr Health J
Rubin, Ross, Stephensen, Bohn, Tanumihardjo, Metabolic effects of inflammation on vitamin A and carotenoids in humans and animal models, Adv Nutr
Sanderson, Spiller, Bowden, Testing and correcting for weak and pleiotropic instruments in two-sample multivariable mendelian randomization, Stat Med
Sarohan, COVID-19: endogenous retinoic acid theory and retinoic acid depletion syndrome, Med Hypotheses
Sarohan, Kizil, Inkaya, Mahmud, Akram et al., A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder, Cell Signal
Shoemark, Colenso, Toelzer, Gupta, Sessions et al., Molecular simulations suggest vitamins, retinoids and steroids as ligands of the free fatty acid Pocket of the SARS-CoV-2 spike Protein*, Angewandte Chemie
Skrivankova, Richmond, Woolf, Davies, Swanson et al., Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration, BMJ
Steinhoff, Lass, Schupp, Biological functions of RBP4 and its relevance for Human diseases, Front Physiol
Stephensen, Lietz, Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2, Br J Nutr
Sun, Maranville, Peters, Stacey, Staley et al., Genomic atlas of the human plasma proteome, Nature
Szymanski, Skopek, Palusinska, Schenk, Stengel et al., Retinoic acid and its derivatives in skin, Cells
Tepasse, Vollenberg, Fobker, Kabar, Schmidt et al., Vitamin A plasma levels in COVID-19 patients: a prospective Multicenter Study and Hypothesis, Nutrients
Trasino, A role for retinoids in the treatment of COVID-19?, Clin Exp Pharmacol Physiol
Verbanck, Chen, Neale, Do, Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases, Nat Genet
Vollenberg, Tepasse, Fobker, Husing-Kabar, Significantly reduced Retinol binding protein 4 (RBP4) levels in critically ill COVID-19 patients, Nutrients
Zhu, Li, Wu, Yu, Li et al., Clinical significance and function of RDH16 as a tumor-suppressing gene in hepatocellular carcinoma, Hepatol Res
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' <jats:title>Background</jats:title>\n'
' <jats:p>The Corona Virus Disease 2019 (COVID-19) pandemic has struck '
'globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally '
'associated with the risk of COVID-19 remains unestablished. We conducted a two-sample '
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' <jats:title>Methods</jats:title>\n'
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' </jats:sec><jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>The MR estimates showed that retinol was associated with lower '
'COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53–0.90, P: 0.0065), whereas the '
'associations between retinol and COVID-19 hospitalization or severity were not significant. '
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'pleiotropic instruments in two-sample multivariable mendelian '
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'Vitamin A plasma levels in COVID-19 patients: a prospective Multicenter '
'Study and Hypothesis. Nutrients. 2021;13(7).',
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'ligands of the free fatty acid Pocket of the SARS-CoV-2 spike Protein*. '
'Angewandte Chemie (International ed in English). 2021;60(13):7098–110.',
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